Alzheimer's Disease Research Center at Columbia University
Principal Investigator: Scott A Small
Abstract: The ADRC at Columbia seeks to advance and disseminate knowledge of the causes, prevention and treatment of Alzheimer's Disease and other age-related dementing disorders. To do this, we maintain and follow a multi-ethnic and multi-racial patient population of normal elderly and the elderly with cognitive disorders to establish the natural history of the disease as a function of age and of genetic makeup. In this application we propose to use a variety of neuropsychological, neurological and imaging tools to examine the earliest stages of AD and to follow these subjects throughout their lives and to compare them to other dementing diseases. A comprehensive neuropathologic examination will be performed on the deceased participants correlated with the clinical, radiological and genetic data. Tissues and DNA obtained from these subjects will be available for research on the biology and genetics of the disease. Individual research projects within the ADRC will examine various aspects of the cellular and molecular biology of AD with emphasis on lipids, on retromer function and on the relationship of GBA mutations to dementia. Patients enrolled in the ADRC will have the opportunity to participate in trials of new drugs and treatments for dementing diseases as they become available. The well-documented cognitive status of these patients makes them highly suitable for inclusion in clinical trials. The Education and Information Core of the Columbia ADRC endeavors to educate both lay and medical communities about AD, about the latest advances in research and about the care of the AD patient. The ADRC serves as a resource for scientists with Columbia as well as outside of it, encouraging new research avenues by the award of pilot grants, by providing tissues and other biological samples, by providing access to a carefully documented patient population and by numerous seminars and Clinical Pathological Correlation Conferences. The Genetics Core serves as the major organizer of family recruitment and identification across the ADRCs and ADCs as well as resources for genotyping and gene expression studies. HIPAA compliant data organization and statistical consulting services are provided under the ADRC to the research community at Columbia and external to it.
Funding Period: 1997-06-15 - 2015-05-31
more information: NIH RePORT
Publications174 found, 100 shown here
- Comprehensive search for Alzheimer disease susceptibility loci in the APOE regionGyungah Jun
Department of Medicine Biomedical Genetics, Boston University Schools of Medicine and Public Health, Boston, MA, USA
Arch Neurol 69:1270-9. 2012....
- Native mutant huntingtin in human brain: evidence for prevalence of full-length monomerEllen Sapp
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA
J Biol Chem 287:13487-99. 2012..Thus, native mutant htt occurs in brain and primary neurons as a soluble full-length monomer...
- Anti-N-methyl-D-aspartate receptor encephalitis: an emerging cause of centrally mediated sinus node dysfunctionTamim M Nazif
Division of Cardiology, Department of Medicine, Columbia University Medical Center, Columbia University, 630 W 168th Street, New York, NY 10032, USA
Europace 14:1188-94. 2012..The prevalence, nature, and outcomes of cardiac dysrhythmias in patients with NMDARE have not been well described...
- Inhibitory effect of dietary lipids on chaperone-mediated autophagyJose Antonio Rodriguez-Navarro
Department of Developmental and Molecular Biology, Institute for Aging Studies, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA
Proc Natl Acad Sci U S A 109:E705-14. 2012..Our findings identify a previously unknown negative impact of high dietary lipid intake on CMA and underscore the importance of diet composition on CMA malfunction in aging...
- Clinical and pathological characteristics of LRRK2 G2019S patients with PDMarkos Poulopoulos
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
J Mol Neurosci 47:139-43. 2012..However, the extent of cortical involvement is variable. Larger longitudinal follow-up of LRRK2 G2019S mutation carriers is required to assess for risk factors for cortical involvement and dementia...
- Comparative lipidomic analysis of mouse and human brain with Alzheimer diseaseRobin B Chan
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10032, USA
J Biol Chem 287:2678-88. 2012..Overall, our study highlights the hypothesis generating potential of lipidomics and identifies novel region-specific lipid anomalies potentially linked to AD pathogenesis...
- Blood-based biomarkers for Alzheimer's disease: plasma Aβ40 and Aβ42, and genetic variantsRichard Mayeux
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, The Gertrude H Sergievsky Center, and the Department of Neurology, Psychiatry, and Epidemiology, Columbia University, New York, NY, USA
Neurobiol Aging 32:S10-9. 2011..Thus, there are several types of peripheral biomarkers under investigation, but more work is required before they can be deemed clinically useful...
- Seizures and epilepsy in Alzheimer's diseaseDaniel Friedman
New York University Comprehensive Epilepsy Center, New York, NY 10016, USA
CNS Neurosci Ther 18:285-94. 2012..We conclude that the literature on seizures and epilepsy in AD, including diagnosis, risk factors, and response to treatment suffers from methodological limitations and gaps...
- Genome-wide association study of Alzheimer's disease with psychotic symptomsP Hollingworth
Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Neurosciences and Mental Health Research Institute, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK
Mol Psychiatry 17:1316-27. 2012..These findings warrant further investigation in larger, appropriately powered samples in which the presence of psychotic symptoms in AD has been well characterized...
- Translational research in neurology: dementiaLawrence S Honig
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Gertrude H Sergievsky Center, New York, New York, USA
Arch Neurol 69:969-77. 2012....
- Analysis of copy number variation in Alzheimer's disease: the NIALOAD/ NCRAD Family StudyShanker Swaminathan
Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine, Indianapolis, IN, USA
Curr Alzheimer Res 9:801-14. 2012..Replication in independent samples as well as further analyses of these gene regions is warranted...
- Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: correlating 7 tesla MRI and pathologyJustin Y Kwan
National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, United States of America
PLoS ONE 7:e35241. 2012..These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia...
- Cross-linking of cell surface amyloid precursor protein leads to increased β-amyloid peptide production in hippocampal neurons: implications for Alzheimer's diseaseRoger Lefort
Taub Institute for Research on Alzheimer s Disease and the Aging Brain and Department of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA
J Neurosci 32:10674-85. 2012..Together, our data suggest the occurrence of a positive pathogenic feedback loop involving Aβ and APP in affected neurons possibly allowing Aβ to spread to nearby healthy neurons...
- Lessons from epidemiologic research about risk factors, modifiers, and progression of late onset Alzheimer's Disease in New York City at Columbia University Medical CenterDevangere Devanand
Department of Psychiatry, Columbia University Medical Center, New York, NY 10032, USA
J Alzheimers Dis 33:S447-55. 2013..These studies have advanced our knowledge about risk factors, modifiers, and progression of late onset Alzheimer's disease..
- Association of shorter leukocyte telomere repeat length with dementia and mortalityLawrence S Honig
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA
Arch Neurol 69:1332-9. 2012..Shortening of chromosomal telomeres is a consequence of cell division and is a biological factor related to cellular aging and potentially to more rapid organismal biological aging...
- The MAPT H1 haplotype is associated with tangle-predominant dementiaIsmael Santa-Maria
Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University, New York 10032, USA
Acta Neuropathol 124:693-704. 2012..These results support the hypothesis that haplotype-specific variation in the MAPT 3' UTR underlies an Aβ-independent mechanism for neurodegeneration in TPD...
- Type 2 diabetes and ethnic disparities in cognitive impairmentJames M Noble
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA
Ethn Dis 22:38-44. 2012..We explored whether ethnic differences in type 2 diabetes (T2D) explain ethnic disparities in cognitive impairment...
- New approaches to genetic counseling and testing for Alzheimer's disease and frontotemporal degenerationJill S Goldman
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, 630 W 168th St, P and S Box 16, New York, NY 10032, USA
Curr Neurol Neurosci Rep 12:502-10. 2012..This article will review current knowledge on the genetics of AD and FTD and suggest clinical guidelines for helping families to navigate through these complexities. The implications of future discoveries will be offered...
- Brain expression genome-wide association study (eGWAS) identifies human disease-associated variantsFanggeng Zou
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA
PLoS Genet 8:e1002707. 2012..Our findings have implications for the design and interpretation of eGWAS in general and the use of brain expression quantitative trait loci in the study of human disease genetics...
- Genotype patterns at PICALM, CR1, BIN1, CLU, and APOE genes are associated with episodic memoryS Barral
Gertrude H Sergievsky Center, The Taub Institute for Research on Alzheimer s Disease and the Aging Brain and the Department ofNeurology, Columbia University College of Physicians and Surgeons, New York, NY, USA
Neurology 78:1464-71. 2012..An alternative approach is the use of multilocus genotype patterns (MLGPs) that combine SNPs at different susceptibility genes...
- Plasma Aβ and PET PiB binding are inversely related in mild cognitive impairmentD P Devanand
Divisions of Geriatric Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY 10032, USA
Neurology 77:125-31. 2011..To evaluate the relations between PET Pittsburgh compound B (PiB-PET) binding (amyloid imaging) and plasma Aβ in patients with mild cognitive impairment (MCI) and similarly aged controls...
- Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activityKai Hui Sun
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Neurochem 118:902-14. 2011..Given the critical role of oxidative stress in AD pathogenesis, an increase in GSTP1 level may be an alternative way to modulate Cdk5 signaling, eliminate oxidative stress, and prevent neurodegeneration...
- Variably protease-sensitive prionopathy: a novel disease of the prion proteinPierluigi Gambetti
Department of Pathology, National Prion Disease Pathology Surveillance Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA
J Mol Neurosci 45:422-4. 2011..These findings suggest that VPSPr is basically different from classical prion diseases such as sCJD being perhaps more akin to other neurodegenerative dementias...
- Hippocampal subregions differentially associate with standardized memory testsAdam M Brickman
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
Hippocampus 21:923-8. 2011....
- (99m)Tc hexamethyl-propylene-aminoxime single-photon emission computed tomography prediction of conversion from mild cognitive impairment to Alzheimer diseaseD P Devanand
NYSPI, Columbia University, New York, NY 10032, USA
Am J Geriatr Psychiatry 18:959-72. 2010..To examine the utility of single-photon emission computed tomography (SPECT) to predict conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD)...
- Plasma ß-amyloid and cognitive declineStephanie A Cosentino
The Gertrude H Sergievsky Center, Taub Institute for Research in Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA
Arch Neurol 67:1485-90. 2010..To determine if plasma β-amyloid (Aβ) levels (1) can be linked to specific cognitive changes that constitute conversion to Alzheimer disease (AD) and (2) correspond to cognitive change independent of dementia...
- Meta-analysis confirms CR1, CLU, and PICALM as alzheimer disease risk loci and reveals interactions with APOE genotypesGyungah Jun
Department of Medicine, Boston University, USA
Arch Neurol 67:1473-84. 2010..To determine whether genotypes at CLU, PICALM, and CR1 confer risk for Alzheimer disease (AD) and whether risk for AD associated with these genes is influenced by apolipoprotein E (APOE) genotypes...
- Variably protease-sensitive prionopathy: a new sporadic disease of the prion proteinWen Quan Zou
Department of Pathology, National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH 44106, USA
Ann Neurol 68:162-72. 2010..The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV)...
- Mitochondrial loss, dysfunction and altered dynamics in Huntington's diseaseJinho Kim
Geriatric Research Education Clinical Center, New England Veterans Administration VISN 1, Bedford, MA 01730, USA
Hum Mol Genet 19:3919-35. 2010..These findings provide further evidence that mitochondrial dysfunction plays a critical role in the pathogenesis of HD...
- Telephone assessment of cognitive function in the late-onset Alzheimer's disease family studyRobert S Wilson
Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL 60612, USA
Arch Neurol 67:855-61. 2010..Administration of cognitive test batteries by telephone has been shown to be a valid and cost-effective means of assessing cognition, but it remains relatively uncommon in epidemiological research...
- Hormonal influences on cognition and risk for Alzheimer's diseaseSarah C Janicki
G H Sergievsky Center, Columbia University Medical Center, 622 West 168th Street, PH 19, New York, NY 10019, USA
Curr Neurol Neurosci Rep 10:359-66. 2010..Future trials are needed to determine whether alternate timing, dosage, formulation, or method of administration of hormone replacement can reduce the risk of dementia...
- SCFFbx2-E3-ligase-mediated degradation of BACE1 attenuates Alzheimer's disease amyloidosis and improves synaptic functionBing Gong
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA
Aging Cell 9:1018-31. 2010..Our study is the first to suggest that promoting Fbx2 in the brain may represent a novel strategy for the treatment of AD...
- Heritability of different forms of memory in the Late Onset Alzheimer's Disease Family StudyRobert S Wilson
Rush Alzheimer s Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
J Alzheimers Dis 23:249-55. 2011..This suggests that genetic analyses of memory endophenotypes may help to identify genetic variants associated with AD...
- Molecular biology and pathology of prion strains in sporadic human prion diseasesPierluigi Gambetti
Department of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH, 44106, USA
Acta Neuropathol 121:79-90. 2011..However, the intrinsic characteristics that distinguish at least four of these strains remain to be identified...
- Huntington's disease - neuropathologyJean Paul G Vonsattel
Department of Pathology, Presbyterian Hospital and Columbia University, New York, NY 10032, USA
Handb Clin Neurol 100:83-100. 2011..In particular, factors promoting apoptosis, and phenomena causing the toxic aggregation of proteins, or the blockage of trophic factors, or mitochondria dysfunction, and excitoxicity have been studied...
- Genetic and clinical features of progranulin-associated frontotemporal lobar degenerationAlice S Chen-Plotkin
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA
Arch Neurol 68:488-97. 2011..To assess the relative frequency of unique mutations and their associated characteristics in 97 individuals with mutations in progranulin (GRN), an important cause of frontotemporal lobar degeneration (FTLD)...
- Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's diseaseAdam C Naj
The John P Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA
Nat Genet 43:436-41. 2011..3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility...
- Importance of symptomatic cerebral infarcts on cognitive performance in patients with Alzheimer's diseaseSoo Jin Cho
Department of Neurology, Hangang Sacred Heart Hospital, Hallym University College of Medicine, 12 Beodnamu ro 7 gil, Seoul, Korea
J Korean Med Sci 26:412-6. 2011..05). The influence of cerebral infarcts is neither general nor diffuse, and the presence of clinical history may have a more important influence on executive performance in AD...
- Genome-wide association of familial late-onset Alzheimer's disease replicates BIN1 and CLU and nominates CUGBP2 in interaction with APOEEllen M Wijsman
Division of Medical Genetics, University of Washington, Seattle, Washington, United States of America
PLoS Genet 7:e1001308. 2011..We suggest that similar adjustments may also be needed for many other large multi-site studies...
- BACE1 retrograde trafficking is uniquely regulated by the cytoplasmic domain of sortilinGINA M FINAN
Graduate Program in Pathobiology and Molecular Medicine, Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA
J Biol Chem 286:12602-16. 2011..g. SorCs1b and SorLA), plays a unique role in BACE1 trafficking. Our studies suggest a new function for sortilin as a modulator of BACE1 retrograde trafficking and subsequent generation of Aβ...
- Phospholipase d2 ablation ameliorates Alzheimer's disease-linked synaptic dysfunction and cognitive deficitsTiago Gil Oliveira
Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, New York 10032, USA
J Neurosci 30:16419-28. 2010..Collectively, our results point to specific molecular species of PA as key modulators of AD pathogenesis and identify PLD2 as a novel potential target for therapeutics...
- Exome sequencing reveals VCP mutations as a cause of familial ALSJanel O Johnson
Neuromuscular Diseases Research Group, Laboratory of Neurogenetics, Porter Neuroscience Building, NIA, NIH, Bethesda, MD 20892, USA
Neuron 68:857-64. 2010....
- Role of mitochondrial amyloid-beta in Alzheimer's diseaseJohn Xi Chen
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
J Alzheimers Dis 20:S569-78. 2010....
- Bezafibrate administration improves behavioral deficits and tau pathology in P301S miceMagali Dumont
Department of Neurology and Neuroscience, Weill Cornell Medical College, New York, NY 10065, USA
Hum Mol Genet 21:5091-105. 2012..Bezafibrate is therefore a promising agent for the treatment of neurodegenerative diseases associated with tau pathology...
- Miniature neurotransmission regulates Drosophila synaptic structural maturationBen Jiwon Choi
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA Center for Motor Neuron Biology and Disease, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Neuron 82:618-34. 2014..Our results establish that miniature neurotransmission, a universal but often-overlooked feature of synapses, has unique and essential functions in vivo...
- Parkinson's disease with Lewy bodies associated with a heterozygous PARKIN dosage mutationMadeleine E Sharp
Department of Neurology, Columbia University, New York, New York, USA
Mov Disord 29:566-8. 2014..Only one other heterozygote PARKIN carrier with autopsy findings has been described. Our case adds to the broadening pathological and clinical phenotype of PARKIN-related disease...
- Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's diseaseUsman A Khan
1 Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, New York, USA 2 Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA 3 Program in Neural and Behavioral Science, State University of New York Downstate Medical Center, Brooklyn, New York, USA
Nat Neurosci 17:304-11. 2014....
- Donepezil treatment of older adults with cognitive impairment and depression (DOTCODE study): clinical rationale and designGregory H Pelton
Division of Geriatric Psychiatry, New York State Psychiatric Institute, NY, USA Department of Psychiatry, College of Physicians and Surgeons, Columbia University, NY, USA
Contemp Clin Trials 37:200-8. 2014..Apolipoprotein E ε4 status, odor identification deficits, and MRI entorhinal/hippocampal cortex atrophy at baseline are evaluated as neurobiological moderators of donepezil treatment effects...
- Alzheimer's disease: analyzing the missing heritabilityPerry G Ridge
Department of Biology, Brigham Young University, Provo, Utah, United States of America ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, Utah, United States of America
PLoS ONE 8:e79771. 2013..Based on our findings and the current direction of human genetics research, we suggest specific study designs for future studies to identify the remaining heritability of Alzheimer's disease. ..
- Screening assay for small-molecule inhibitors of synaptojanin 1, a synaptic phosphoinositide phosphataseLaura Beth J McIntire
1Department of Pathology and Cell Biology, and the Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, NY, USA
J Biomol Screen 19:585-94. 2014..The assay will enable identification of novel Synj1 inhibitors that have potential utility as chemical probes to dissect the cellular role of Synj1 as well as potential to prevent or reverse AD-associated synaptic abnormalities. ..
- Review of lipid and lipoprotein(a) abnormalities in childhood arterial ischemic strokeSally M Sultan
Neurologic Institute, Department of Neurology, Columbia University Medical Center, New York, NY, USA
Int J Stroke 9:79-87. 2014..The literature suggests that elevated lipoprotein (a) may be more likely in children with arterial ischemic stroke than in control children. The absence of confirmatory study on dyslipidemia should be addressed with future research. ..
- Presenting neuropsychological testing profile of autopsy-confirmed frontotemporal lobar degenerationHiroshi Yoshizawa
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, N Y, USA
Dement Geriatr Cogn Disord 36:279-89. 2013..We aimed to investigate how neuropsychological test measures at presentation might differentiate frontotemporal lobar degeneration (FTLD) from Alzheimer's disease (AD)...
- Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkersChristiane Reitz
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY, United States Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, United States Gertrude H Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, United States
Biochem Pharmacol 88:640-51. 2014..In this review article, we provide an overview of the epidemiology of AD, review the biomarkers that may be used for risk assessment and in diagnosis, and give suggestions for future research. ..
- Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS)Ping An
Department of Genetics Division of Statistical Genomics, Washington University School of Medicine, St Louis, MO, USA Electronic address
Metabolism 63:461-8. 2014....
- Characterization and molecular profiling of PSEN1 familial Alzheimer's disease iPSC-derived neural progenitorsAndrew A Sproul
The New York Stem Cell Foundation, New York, New York, United States of America
PLoS ONE 9:e84547. 2014..Therefore, in our PSEN1 iPSC model, we have reconstituted an essential feature in the molecular pathogenesis of FAD, increased generation of Aβ42/40, and have characterized novel expression changes. ..
- Pharmacological chaperones stabilize retromer to limit APP processingVincent J Mecozzi
1 Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts, USA 2 Department of Chemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Masschusetts, USA 3
Nat Chem Biol 10:443-9. 2014..These findings show that pharmacological chaperones can enhance the function of a multiprotein complex and may have potential therapeutic implications for neurodegenerative diseases. ..
- Alzheimer's-related changes in non-demented essential tremor patients vs. controls: links between tau and tremor?Jie J Pan
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
Parkinsonism Relat Disord 20:655-8. 2014..Moreover, in a brain repository-based study, a larger than expected proportion of ET patients also developed pathological changes characteristic of progressive supranuclear palsy, further suggesting a link between ET and tau pathology...
- Absence of C9ORF72 expanded or intermediate repeats in autopsy-confirmed Parkinson's diseaseKaren Nuytemans
University of Miami, Miller School of Medicine, John P Hussman Institute for Human Genomics, Miami, Florida, USA
Mov Disord 29:827-30. 2014..Because 10% to 25% of clinically diagnosed PD have different diagnoses upon autopsy, we hypothesized that this may reflect phenotypic heterogeneity or concomitant pathology of other neurodegenerative disorders...
- Age, gender, and cancer but not neurodegenerative and cardiovascular diseases strongly modulate systemic effect of the Apolipoprotein E4 allele on lifespanAlexander M Kulminski
Center for Population Health and Aging, Duke University, Durham, North Carolina, United States of America Institute for Genome Science and Policy, Duke University, Durham, North Carolina, United States of America Social Science Research Institute, Duke University, Durham, North Carolina, United States of America
PLoS Genet 10:e1004141. 2014..The analyses suggest the existence of age- and gender-sensitive systemic mechanisms linking the e4 allele to lifespan which can non-additively interfere with cancer-related mechanisms...
- Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's diseaseStephen Salloway
From Butler Hospital, Providence, RI S S Brigham and Women s Hospital, Boston R S University College London, Institute of Neurology, London N C F University of Göteborg, Sahlgrenska University Hospital, Molndal, Sweden K B University of Pittsburgh, Pittsburgh W K Veterans Affairs Medical Center, Seattle M R Cleo Roberts Center for Clinical Research Sun Health Research Institute, Sun City, AZ M S Columbia University L S H and New York University Langone Medical Center S F, New York University of Rochester School of Medicine and Dentistry, Rochester, NY A P P Janssen Alzheimer Immunotherapy Research and Development, South San Francisco, CA M R, N K, B N, V G, M M, D W, Y L, I C T, E L, E Y, H R B Janssen Research and Development, Titusville, NJ J L Global R and D Partners and the University of California, San Diego both in San Diego M G and Pfizer, Collegeville, PA R B
N Engl J Med 370:322-33. 2014..Bapineuzumab, a humanized anti-amyloid-beta monoclonal antibody, is in clinical development for the treatment of Alzheimer's disease...
- Hyperleucinemia causes hippocampal retromer deficiency linking diabetes to Alzheimer's diseaseMichael V Morabito
Naomi Berrie Diabetes Center, Division of Molecular Genetics, Department of Pediatrics, College of Physicians and Surgeons, New York, NY, USA
Neurobiol Dis 65:188-92. 2014..Our results suggest that hyperleucinemia may account, in part, for the association of insulin resistance/T2D with AD. ..
- Age-specific incidence rates for dementia and Alzheimer disease in NIA-LOAD/NCRAD and EFIGA families: National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and EstuBadri N Vardarajan
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, New York2Gertrude H Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, New York
JAMA Neurol 71:315-23. 2014..Few reports investigate incidence rates in large family-based studies in which the participants were selected for family history of LOAD...
- Heritability of and mortality prediction with a longevity phenotype: the healthy aging indexJason L Sanders
Graduate School of Public Health, University of Pittsburgh, A527 Crabtree Hall, 130 DeSoto Street, Pittsburgh, PA 15261
J Gerontol A Biol Sci Med Sci 69:479-85. 2014..We investigated the HAI's association with survival in the Cardiovascular Health Study and heritability in the Long Life Family Study...
- Phosphatidylinositol-3-phosphate regulates sorting and processing of amyloid precursor protein through the endosomal systemEtienne Morel
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA
Nat Commun 4:2250. 2013....
- Phenotypic assays for β-amyloid in mouse embryonic stem cell-derived neuronsLaura Beth J McIntire
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032, USA
Chem Biol 20:956-67. 2013..Our approach is therefore highly suitable for phenotypic screening in AD drug discovery and has the potential to identify therapeutic candidates with improved efficacy and safety potential. ..
- Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcificationSandy Chan Hsu
Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
Neurogenetics 14:11-22. 2013..Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation...
- Early neuropsychological discriminants for Lewy body disease: an autopsy seriesHiroshi Yoshizawa
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, NY, USA
J Neurol Neurosurg Psychiatry 84:1326-30. 2013..To determine which neuropsychological test measures and which symptoms at presentation might best differentiate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD)...
- The role of lipids in the control of autophagyClaudia Dall'Armi
Department of Pathology and Cell Biology, Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA
Curr Biol 23:R33-45. 2013..This review summarizes this progress and highlights the role of specific lipids in the various steps of macroautophagy, including the signaling processes underlying macroautophagy initiation, autophagosome biogenesis and maturation...
- Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort studyMaarten J Titulaer
Department of Neurology and Neurosciences, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
Lancet Neurol 12:157-65. 2013..We aimed to assess the presentation of the disease, the spectrum of symptoms, immunotherapies used, timing of improvement, and long-term outcome...
- Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitisDavid C Whitcomb
Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Nat Genet 44:1349-54. 2012..These results could partially explain the high frequency of alcohol-related pancreatitis in men (male hemizygote frequency is 0.26, whereas female homozygote frequency is 0.07)...
- Depressive symptoms are not associated with leukocyte telomere length: findings from the Nova Scotia Health Survey (NSHS95), a population-based studyJonathan A Shaffer
Center for Behavioral Cardiovascular Health, Columbia University, New York, New York, United States of America
PLoS ONE 7:e48318. 2012....
- Reduction of synaptojanin 1 ameliorates synaptic and behavioral impairments in a mouse model of Alzheimer's diseaseLaura Beth J McIntire
Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University Medical Center, New York, New York 10032, USA
J Neurosci 32:15271-6. 2012..Our work expands on recent studies identifying lipid metabolism and lipid-modifying enzymes as targets of AD-associated synaptic and behavioral impairment...
- Initial assessment of the pathogenic mechanisms of the recently identified Alzheimer risk LociPatrick Holton
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK
Ann Hum Genet 77:85-105. 2013..Although these results are mainly negative, they allow us to start defining more realistic alternative approaches to determine the role of all the genetic loci involved in Alzheimer's disease...
- Relation between leukocyte telomere length and incident coronary heart disease events (from the 1995 Canadian Nova Scotia Health Survey)Siqin Ye
Center for Behavioral Cardiovascular Health, Department of Medicine, Columbia University, New York, NY, USA
Am J Cardiol 111:962-7. 2013..25, 95% confidence interval 0.82 to 1.90, p = 0.30). In conclusion, these findings do not support a linear association between leukocyte telomere length and incident CHD risk in the general population...
- RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease riskDavid A MacLeod
Department of Neurology and Taub Institute, Columbia University, Black Building 1208, 650 West 168th Street, New York, NY 10032, USA
Neuron 77:425-39. 2013..Expression of wild-type VPS35, but not a familial PD-associated mutant form, rescued these defects. Taken together, these studies implicate retromer and lysosomal pathway alterations in PD risk...
- Caspase-2 is required for dendritic spine and behavioural alterations in J20 APP transgenic miceJulio Pozueta
Department of Pathology and Cell Biology and The Taub Institute for Research on Alzheimer s Disease and the Aging Brain v, Columbia University, New York, NY 10032, USA
Nat Commun 4:1939. 2013..These findings directly implicate caspase-2 as key driver of synaptic dysfunction in Alzheimer's disease and offer novel therapeutic targets...
- Familial aggregation of cranial tremor in familial essential tremorElan D Louis
G H Sergievsky Center, New York, N Y, USA
Neuroepidemiology 41:48-53. 2013..Cranial (neck, voice, and jaw) tremor is an important feature of ET. We examined whether cranial tremor aggregates in ET families, after controlling for other factors (age, tremor severity, and duration)...
- Independent and epistatic effects of variants in VPS10-d receptors on Alzheimer disease risk and processing of the amyloid precursor protein (APP)C Reitz
The Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University, New York, NY, USA
Transl Psychiatry 3:e256. 2013..More importantly, the results indicate that variants within these genes have epistatic effects on AD risk...
- Aromatase variants modify risk for Alzheimer's disease in a multiethnic female cohortS C Janicki
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, New York, N Y, USA
Dement Geriatr Cogn Disord 35:340-6. 2013..We investigated the influence of CYP19 polymorphisms on risk for AD in a multiethnic cohort of women, with individual ethnicity assessed by genetic population ancestry informative markers (AIMs) as well as by self-identified ethnicity...
- A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodiesMichael A Nalls
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA
JAMA Neurol 70:727-35. 2013..While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders...
- Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ϵ4,and the risk of late-onset Alzheimer disease in African AmericansChristiane Reitz
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Gertrude H Sergievsky Center, Columbia University, 630 W 168th St, New York, NY 10032, USA
JAMA 309:1483-92. 2013..Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment...
- SORL1 is genetically associated with late-onset Alzheimer's disease in Japanese, Koreans and CaucasiansAkinori Miyashita
Department of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
PLoS ONE 8:e58618. 2013..Our study highlights the importance of examining associations in multiple ethnic populations...
- Interplay of LRRK2 with chaperone-mediated autophagySamantha J Orenstein
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, USA
Nat Neurosci 16:394-406. 2013..This newly described LRRK2 self-perpetuating inhibitory effect on CMA could underlie toxicity in Parkinson's disease by compromising the degradation of α-synuclein, another Parkinson's disease-related protein degraded by this pathway...
- Genetic analysis of the FUS/TLS gene in essential tremorN Parmalee
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Columbia University, New York, NY 10044, USA
Eur J Neurol 20:534-9. 2013..Q290X) in the amyotrophic lateral sclerosis (ALS) gene fused in sarcoma/translated in liposarcoma (FUS/TLS) was identified by exome sequencing. No confirmatory studies have been published...
- Reduced Purkinje cell number in essential tremor: a postmortem studyJordan E Axelrad
Gertrude H Sergievsky Center, Columbia University, New York, New York, USA
Arch Neurol 65:101-7. 2008..In recent postmortem studies, we documented increased numbers of torpedoes (Purkinje cell axonal swellings) in ET patients without Lewy bodies. Purkinje cell loss, however, has never been rigorously assessed...
- Amyloid-beta-induced mitochondrial dysfunctionJohn Xi Chen
Harvey Cushing Institutes of Neuroscience, North Shore Long Island Jewish Health System, Great Neck, NY 11021, USA
J Alzheimers Dis 12:177-84. 2007..Thus, blockade of ABAD/Abeta interaction may be a potential therapeutic strategy for AD...
- Laboratory biomarkers in Alzheimer's diseaseJoshua R Steinerman
Taub Institute for Research on Alzheimer s Disease and the Aging Brain, Gertrude H Sergievsky Center, Columbia University College of Physician and Surgeons, 630 West 168th Street, New York, NY 10032, USA
Curr Neurol Neurosci Rep 7:381-7. 2007..In this review, we focus on biomarkers in cerebrospinal fluid and plasma, including measurements of the proteins tau and beta-amyloid...
- GAB2 alleles modify Alzheimer's risk in APOE epsilon4 carriersEric M Reiman
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
Neuron 54:713-20. 2007..Our findings suggest that GAB2 modifies LOAD risk in APOE epsilon4 carriers and influences Alzheimer's neuropathology...
- Interaction of amyloid binding alcohol dehydrogenase/Abeta mediates up-regulation of peroxiredoxin II in the brains of Alzheimer's disease patients and a transgenic Alzheimer's disease mouse modelJun Yao
Department of Pathology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032, USA
Mol Cell Neurosci 35:377-82. 2007..Therefore this indicates the possibility of reversing changes observed in Alzheimer's disease and that the Abeta-ABAD interaction is a suitable drug target...
- Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypesJ C Schymick
Laboratory of Neurogenetics, National Institute of Aging, NIH, Bethesda, Maryland, USA
J Neurol Neurosurg Psychiatry 78:754-6. 2007..Clinical and pathological overlap between amyotrophic lateral sclerosis (ALS) and FTD prompted us to screen PGRN in patients with ALS and ALS-FTD...
- Reelin depletion in the entorhinal cortex of human amyloid precursor protein transgenic mice and humans with Alzheimer's diseaseJeannie Chin
Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, California 94158, USA
J Neurosci 27:2727-33. 2007..We conclude that alterations in Reelin processing or signaling may be involved in AD-related neuronal dysfunction...
- Hippocampal and entorhinal atrophy in mild cognitive impairment: prediction of Alzheimer diseaseD P Devanand
Department of Biological Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
Neurology 68:828-36. 2007..To evaluate the utility of MRI hippocampal and entorhinal cortex atrophy in predicting conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD)...
- Alterations in lipid metabolism gene expression and abnormal lipid accumulation in fibroblast explants from giant axonal neuropathy patientsConrad L Leung
Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
BMC Genet 8:6. 2007..The goal of this study was to examine global alterations in gene expression in fibroblasts derived from newly identified GAN families compared with normal cells...
- Objective metamemory testing captures awareness of deficit in Alzheimer's diseaseStephanie Cosentino
Cognitive Neuroscience Division, Taub Institute, Columbia University Medical Center, New York, NY 10032, USA
Cortex 43:1004-19. 2007....
- Prion: the chameleon proteinW Q Zou
Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH 44106, USA
Cell Mol Life Sci 64:3266-70. 2007..Recent progress in modeling prion diseases and characterization of the various prion protein forms reveal that such a wide spectrum of the diseases is associated with the chameleon-like conformational features of prions...
- Association between genetic variants in SORL1 and autopsy-confirmed Alzheimer diseaseJ H Lee
Gertrude H Sergievsky Center, Columbia University, 630 W 168 St, New York, NY 10032, USA
Neurology 70:887-9. 2008
- Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prionsJ Yuan
Department of Pathology and National Prion Disease Pathology Surveillance Center, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA
Cell Mol Life Sci 65:631-43. 2008..Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases...
- Endophilin I expression is increased in the brains of Alzheimer disease patientsYimin Ren
Schools of Biology and Medicine, University of St Andrews, Scotland KY16 9TS
J Biol Chem 283:5685-91. 2008..Therefore this identifies endophilin I as a new indicator of the progression of Alzheimer disease...
- Massachusetts Alzheimer's Disease Research CenterBradley T Hyman; Fiscal Year: 2013..Going forward, the MADRC will continue to expand its clinical and neuropathological resources, its innovative training and scientific programs directed toward AD research. ..
- Alzheimer's Disease Research CenterOscar L Lopez; Fiscal Year: 2013..Alzheimer's centers such as the one in Pittsburgh play a critical role in the nation's struggle to: 1) care for those currently afflicted;2) improve diagnosis and treatment;and 3) find a means of prevention. ..
- UCLA Alzheimer's Disease Research CenterDavid B Teplow; Fiscal Year: 2013..Innovations in advancing research are proposed in each Core of this proposal. Each core has responded to criticisms and recommendations from the 2008 review in this renewal application. ..
- Emory Alzheimer's Disease CenterAllan I Levey; Fiscal Year: 2013..abstract_text> ..
- New Approaches to Dementia HeterogeneityBruce L Miller; Fiscal Year: 2013..Finally, we will create ideal data management approaches for neurodegenerative conditions that will be shared with other ADRCs, beginning with UC-Davis. ..