- The uncertain anatomy of Alzheimer's diseaseJohn Hardy
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Room 6C103, Building 10, MSC1589, Bethesda, MD 20892, USA
Neurobiol Aging 25:719-20; discussion 743-6. 2004
- Genetic variation in the tau protein phosphatase-2A pathway is not associated with Alzheimer's disease riskJosé L Vázquez-Higuera
Neurology Service and CIBERNED, Marqués de Valdecilla University Hospital University of Cantabria and IFIMAV, Santander, Spain
BMC Res Notes 4:327. 2011..abstract:..
- Caspase-1 genetic variation is not associated with Alzheimer's disease riskJosé Luis Vázquez-Higuera
Neurology Service and CIBERNED, Marques de Valdecilla University Hospital, Santander, Spain
BMC Med Genet 11:32. 2010..CASP1 genetic variation (G+7/in6A, rs501192) has been associated with susceptibility to myocardial infarction and cardiovascular death risk. We examined the contribution of this gene to the susceptibility for AD...
- DYRK1A genetic variants are not linked to Alzheimer's disease in a Spanish case-control cohortJosé Luis Vázquez-Higuera
Neurology Service and CIBERNED, Marques de Valdecilla University Hospital, University of Cantabria, Santander, Spain
BMC Med Genet 10:129. 2009....
- Presenilin 1 mutation in an african american family presenting with atypical Alzheimer dementiaGregory A Rippon
Department of Neurology, Mayo Clinic, Rochester, MN, USA
Arch Neurol 60:884-8. 2003..Mutations in 3 genes (presenilin 1 and 2 and amyloid precursor protein) are associated with presenile AD. Presenilin 1 gene mutations have not been described in African Americans...
- The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeuticsJohn Hardy
Laboratories of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
Science 297:353-6. 2002..The rest of the disease process, including formation of neurofibrillary tangles containing tau protein, is proposed to result from an imbalance between Abeta production and Abeta clearance...
- Amyloid at the blood vessel wallJohn Hardy
Nat Med 12:756-7. 2006
- Problems and solutions in the genetic analysis of late-onset Alzheimer's diseaseJohn Hardy
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892 3707, USA
Neurodegener Dis 1:213-7. 2004..In this article, we discuss the complexity of the problem and the pitfalls in the analytical methods that have been used and how we are approaching this problem...
- Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's diseaseAndreas Papassotiropoulos
Division of Psychiatry Research, University of Zurich, Zurich, Switzerland
Neurodegener Dis 2:233-41. 2005....
- Alzheimer's disease: the amyloid cascade hypothesis: an update and reappraisalJohn Hardy
Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, 35, Convent Drive, Bethesda, MD20892, USA
J Alzheimers Dis 9:151-3. 2006..Here I recap the scientific and personal background of the delineation of the amyloid cascade hypothesis for Alzheimer's disease that I wrote with Gerry Higgins and the events leading to the writing of that influential review...
- Association of HFE common mutations with Parkinson's disease, Alzheimer's disease and mild cognitive impairment in a Portuguese cohortRita J Guerreiro
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, USA
BMC Neurol 6:24. 2006..Several reports have tested the association of HFE variants with neurodegenerative diseases, such as AD and PD with conflicting results...
- The genetics of neurodegenerative diseasesJohn Hardy
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland 20892, USA
J Neurochem 97:1690-9. 2006..This mechanistic understanding is now leading to therapeutic strategies based on this new understanding. As yet, however, no mechanistic therapies are in use in the clinic...
- Frontal temporal dementia: dissecting the aetiology and pathogenesisJohn Hardy
Laboratory of Neurogenetics, National Institute on Aging, National Institute of Mental Health, Porter Neuroscience Building, 35 Convent Drive, Bethesda, MD, USA
Brain 129:830-1. 2006
- Tangle diseases and the tau haplotypesJohn Hardy
Laboratory of Neurogenetics, National Institutes on Aging and of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, MD 20852, USA
Alzheimer Dis Assoc Disord 20:60-2. 2006..We discuss the reason for this disequilibrium, its evolutionary history, and the role of genetic variability at MAPT in the etiology of tauopathies...
- Has the amyloid cascade hypothesis for Alzheimer's disease been proved?John Hardy
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A1015, 35 Convent Drive, Room 1A1015 MSC 3707, Bethesda, MD 20892 3707, USA
Curr Alzheimer Res 3:71-3. 2006..In this article, I summarize the major pieces of evidence adduced to support the amyloid cascade hypothesis and point out their limitations...
- A presenilin-1 mutation (T245P) in transmembrane domain 6 causes early onset Alzheimer's diseaseTerri Edwards-Lee
Los Angeles Biomedical Research Institute, Harbor UCLA Medical Center, 1124 West Carson Street, Torrance, CA 90502, USA
Neurosci Lett 398:251-2. 2006..The position of the mutation is in the transmembrane domain that harbors the aspartic acid residue which is believed to be part of the active site of gamma-secretase...
- Characterization of two APP gene promoter polymorphisms that appear to influence risk of late-onset Alzheimer's diseaseDebomoy K Lahiri
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, 791 N Union Drive, Indianapolis, IN 46202, USA
Neurobiol Aging 26:1329-41. 2005..Characterization of the activity of a regulatory polymorphism of the APP gene points towards understanding mechanisms that likely underlie the majority of AD cases and may contribute to promoter-based drug design...
- Genetic variability at the LXR gene (NR1H2) may contribute to the risk of Alzheimer's diseaseOmanma Adighibe
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Porter Neuroscience Building, 35 Convent Drive, Bethesda, MD 20892 3707, USA
Neurobiol Aging 27:1431-4. 2006..As part of this analysis, we have assessed the NR1H2 gene on chromosome 19 and report here a modest association with the locus in sibpairs with late onset disease...
- A hundred years of Alzheimer's disease researchJohn Hardy
Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, Bethesda, Maryland 20892, USA
Neuron 52:3-13. 2006..The progress toward effective mechanistic therapy is reviewed...
- Characteristics of frontotemporal dementia patients with a Progranulin mutationEdward D Huey
Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 1440, USA
Ann Neurol 60:374-80. 2006..The range of mutations of PGRN that can result in the FTD phenotype and the clinical presentation of patients with PGRN mutations have yet to be determined...
- The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcriptsAmanda J Myers
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892 3707, USA
Neurobiol Dis 25:561-70. 2007..We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies...
- Neurofibrillary tau pathology modulated by genetic variation of alpha-synucleinTerhi Peuralinna
Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland
Ann Neurol 64:348-52. 2008..These results suggest for the first time that variation of alpha-synuclein modulates neurofibrillary tau pathology and support the recent observations of an interaction of alpha-synuclein and tau in neurodegeneration...
- Parietal lobe deficits in frontotemporal lobar degeneration caused by a mutation in the progranulin geneJonathan D Rohrer
Dementia Research Centre, Institute of Neurology, University College London, London, England
Arch Neurol 65:506-13. 2008..To describe the clinical, neuropsychologic, and radiologic features of a family with a C31LfsX35 mutation in the progranulin gene CCDS11483.1)...
- Sorl1 as an Alzheimer's disease predisposition gene?Jennifer A Webster
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Ariz, USA
Neurodegener Dis 5:60-4. 2008..Here we present the results of our large case-control whole-genome scan at over 500,000 polymorphisms which presents weak evidence for association and potentially narrows the association interval...
- Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's diseaseMarian L Hamshere
Biostatistics and Bioinformatics Unit, School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
Hum Mol Genet 16:2703-12. 2007..Where samples overlapped, the genotyping consistency was high, estimated to average at 97.3%. Our large-scale linkage analysis consolidates clear evidence for a susceptibility locus for LOAD on 10q21.2...
- A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease, seizures and cotton wool plaques, but not spastic paraparesisAntony E Shrimpton
Department of Pathology, SUNY Upstate Medical University, 750 E Adams St, Syracuse, NY 13210, USA
Neuropathology 27:228-32. 2007..p.L420R (g.1508T > G) is the mutation responsible for EOAD, seizures and CWP without SP in this family...
- 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...
- A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's diseaseKeith D Coon
Neurogenomics Division, Translational Genomics Research Institute, Phoenix, Ariz 85004, USA
J Clin Psychiatry 68:613-8. 2007....
- Testing for linkage and association across the dihydrolipoyl dehydrogenase gene region with Alzheimer's disease in three sample populationsAbraham M Brown
Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA
Neurochem Res 32:857-69. 2007..Finally, minimum sample size calculations using parameters from the DLD locus suggest that sample sizes on the order of 1,000 total cases and controls are needed to detect association for a wide range of genetic model parameters...
- Putting presenilins centre stage. Introduction to the Talking Point on the role of presenilin mutations in Alzheimer diseaseJohn Hardy
Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, National Institutes of Health Main Campus, Bethesda, Maryland 20892, USA
EMBO Rep 8:134-5. 2007
- Insulin-degrading enzyme haplotypes affect insulin levels but not dementia riskLauren Marlowe
Laboratorie of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, MD 20892, USA
Neurodegener Dis 3:320-6. 2006..Insulin-degrading enzyme (IDE) polymorphism is hypothesized to regulate insulin levels as well as processes involved in neuronal compromise found in dementia...
- Does Abeta 42 have a function related to blood homeostasis?John Hardy
Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Building, NIH Main Campus, Bethesda, MD 20892, USA
Neurochem Res 32:833-5. 2007..In this review, I discuss the possibility that Abeta42 has a physiologic function in blood vessel homeostasis and the consequences that this might have for theories concerning the pathogenesis of Alzheimer's disease and for treatment...
- The persistence of memoryMark R Cookson
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA
N Engl J Med 355:2697-8. 2006
- Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic miceKavon Rezai-Zadeh
Silver Child Development Center, Department of Psychiatry and Behavioral Medicine, University of South Florida, Tampa, Florida 33613, USA
J Neurosci 25:8807-14. 2005..These data raise the possibility that EGCG dietary supplementation may provide effective prophylaxis for AD...
- Dense-core plaques in Tg2576 and PSAPP mouse models of Alzheimer's disease are centered on vessel wallsSamir Kumar-Singh
Department of Molecular Genetics VIB8, Neurodegenerative Brain Diseases Research Group, Molecular Neuropathology Project, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
Am J Pathol 167:527-43. 2005....
- Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementiaEric M Reiman
Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006, USA
Proc Natl Acad Sci U S A 101:284-9. 2004..Carriers of a common Alzheimer's susceptibility gene have functional brain abnormalities in young adulthood, several decades before the possible onset of dementia...
- Variation in the urokinase-plasminogen activator gene does not explain the chromosome 10 linkage signal for late onset ADAmanda J Myers
Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri, USA
Am J Med Genet B Neuropsychiatr Genet 124:29-37. 2004..Eight polymorphisms spanning the entire gene were examined using case control (CC) and family-based association methods. No association was observed by any method making it unlikely that variation in PLAU explains our linkage data...
- Alzheimer's disease: genetic evidence points to a single pathogenesisJohn Hardy
Ann Neurol 54:143-4. 2003
- The relationship between amyloid and tauJohn Hardy
Laboratory of Neurogenetics, NIA NIH, Building 10, 6C103, Bethesda, MD 20892, USA
J Mol Neurosci 20:203-6. 2003....
- Testing times for the "amyloid cascade hypothesis"John Hardy
Laboratory of Neurogenetics, NIA NIH, Building 10, 6C103, Bethesda, MD 20892, USA
Neurobiol Aging 23:1073-4. 2002
- An association study of a functional catalase gene polymorphism, -262C-->T, and patients with Alzheimer's diseaseAntonis Goulas
Department of Pharmacology, School of Medicine, Aristotle University, Thessaloniki 54124, Greece
Neurosci Lett 330:210-3. 2002..No significant difference has emerged from the comparison of either genotype or allele frequencies (P>0.5). We conclude that the catalase gene -262C-->T polymorphism does not confer a protective effect with respect to AD...
- The tau locus is not significantly associated with pathologically confirmed sporadic Parkinson's diseaseRohan de Silva
Reta Lila Weston Institute of Neurological Studies, Royal Free and University College Medical School, London, UK
Neurosci Lett 330:201-3. 2002....
- Psychotic genes or forgetful ones?Simon Lovestone
Neurology 59:11-2. 2002
- Toxic proteins in neurodegenerative diseaseJ Paul Taylor
Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
Science 296:1991-5. 2002..Increased understanding of the cellular mechanisms for disposal of abnormal proteins and of the effects of toxic protein accumulation on neuronal survival may allow the development of rational, effective treatment for these disorders...
- Apolipoprotein E4 and tau allele frequencies among Choctaw IndiansJ Neil Henderson
Department of Health Promotion Sciences, University of Oklahoma, Oklahoma City 73190, USA
Neurosci Lett 324:77-9. 2002....
- The tau H1 haplotype is associated with Parkinson's disease in the Norwegian populationMatt Farrer
Laboratory of Familial Movement Disorders, Mayo Clinic, Jacksonville, FL, USA
Neurosci Lett 322:83-6. 2002..52; 95% confidence interval: 2.64-11.10; P=2.17x10(-6)). Findings provide evidence that tau participates in the PD pathogenic process and demonstrate the value of isolated populations in mapping complex traits...
- ApoE epsilon3-haplotype modulates Alzheimer beta-amyloid deposition in the brainLiisa Myllykangas
Department of Pathology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
Am J Med Genet 114:288-91. 2002..These results indicate that there is significant allelic variation in the ApoE gene region, which modulates brain amyloid deposition and AD risk, independent of the ApoE protein polymorphism...
- Full genome screen for Alzheimer disease: stage II analysisAmanda Myers
Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA
Am J Med Genet 114:235-44. 2002..Of the seven markers we tested in family-based and case control samples, the only nominally positive association we found was with the 167 bp allele of marker D10S1217 (chi-square=7.11, P=0.045, df=1)...
- Toward Alzheimer therapies based on genetic knowledgeJohn Hardy
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA
Annu Rev Med 55:15-25. 2004....
- CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregationLeonard Petrucelli
Mayo Clinic, Jacksonville, FL 32224, USA
Hum Mol Genet 13:703-14. 2004..Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target...
- An association study of the cholesteryl ester transfer protein TaqI B polymorphism with late onset Alzheimer's diseaseLiana Fidani
Department of General Biology, School of Medicine, Aristotle University, Thessaloniki 54124, Greece
Neurosci Lett 357:152-4. 2004..CETP TaqI B did not interact significantly with either APOE epsilon4 or LPLS447X, in this study...
- Chromosome 21 BACE2 haplotype associates with Alzheimer's disease: a two-stage studyLiisa Myllykangas
Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland
J Neurol Sci 236:17-24. 2005..08). BACE2 haplotype association with AD in two independent datasets provides further evidence for an AD susceptibility locus on chromosome 21q within or close to BACE2...
- Correlations between apolipoprotein E epsilon4 gene dose and brain-imaging measurements of regional hypometabolismEric M Reiman
Positron Emission Tomography Center, Banner Good Samaritan Medical Center, Phoenix, AZ 85006, USA
Proc Natl Acad Sci U S A 102:8299-302. 2005..This study raises the possibility of using PET as a quantitative presymptomatic endophenotype to help evaluate the individual and aggregate effects of putative genetic and nongenetic modifiers of AD risk...
- Association studies between risk for late-onset Alzheimer's disease and variants in insulin degrading enzymePetra Nowotny
Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA
Am J Med Genet B Neuropsychiatr Genet 136:62-8. 2005..Although our results are not universally negative, we were unable to replicate the results of previous studies and conclude that common variants or haplotypes of these variants in IDE are not major risk factors for LOAD...
- The architecture of the tau haplotype block in different ethnicitiesHon Chung Fung
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Building 35, Room 1A1008, MSC 3707, Bethesda, MD 20892, USA
Neurosci Lett 377:81-4. 2005..We discuss this observation in terms of the establishment of the haplotype structure and the possible impact of the tau haplotype on neurodegeneration in humans...
- Genome screen for loci influencing age at onset and rate of decline in late onset Alzheimer's diseasePeter Holmans
Biostatistics and Bioinformatics Unit, Wales College of Medicine, Heath Park, Cardiff, United Kingdom
Am J Med Genet B Neuropsychiatr Genet 135:24-32. 2005..08) and chromosome 9 (max LOD = 3.34). The previously reported genome-wide linkage of AD to chromosome 10 was not influenced by any of the covariates studied...
- Genetic association of the APP binding protein 2 gene (APBB2) with late onset Alzheimer diseaseYonghong Li
Celera Diagnostics, Alameda, California 94502, USA
Hum Mutat 25:270-7. 2005..43 [95% CI: 1.61-3.67]; OR(het)=2.15 [95% CI: 1.46-3.17]; P=0.00006) in the combined sample set. Our data raise the possibility that genetic variations in APBB2 may affect LOAD susceptibility...
- The tau H2 haplotype is almost exclusively Caucasian in originWhitney Evans
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
Neurosci Lett 369:183-5. 2004..We discuss this observation in terms of the origin of the H2 haplotype and the epidemiology of the tauopathies...
- Profile: John HardyBruce Diamond
Nat Med 10:1009. 2004
- Association of the dihydrolipoamide dehydrogenase gene with Alzheimer's disease in an Ashkenazi Jewish populationAbraham M Brown
Dementia Research Service, Burke Medical Research Institute, 785 Mamaroneck Ave, White Plains, New York 10605, USA
Am J Med Genet B Neuropsychiatr Genet 131:60-6. 2004..0009, n = 83) and the Ashkenazi Jewish subseries (P = 0.017, n = 49). The DLD genotype appears to operate independently of APOE in conferring AD risk...
- Is amyloid plaque imaging the key to monitoring brain pathology of Alzheimer's disease in vivo?John Hardy
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, 35 Convent Drive, Room 1A1015 MSC 3707, Bethesda, MD 20892 3707, USA
Eur J Nucl Med Mol Imaging 31:1539-40. 2004
- How many pathways are there to nigral death?John Hardy
Ann Neurol 56:316-8. 2004
- Association of ABCA1 with late-onset Alzheimer's disease is not observed in a case-control studyYonghong Li
Celera Diagnostics, Alameda, CA, USA
Neurosci Lett 366:268-71. 2004..Further, we did not observe significant and replicated association of other ABCA1 SNPs we examined with the disease, thus these ABCA1 variants do not appear to influence the risk of LOAD in this study...
- The structure of the tau haplotype in controls and in progressive supranuclear palsyAlan M Pittman
Reta Lila Weston Institute of Neurological Studies, University College London, UK
Hum Mol Genet 13:1267-74. 2004..We show that the entire, fully extended H1 haplotype is associated with PSP, which implicates several other genes in addition to MAPT, as candidate pathogenic loci...
- Identifying genetic factors in Parkinson diseaseMatt Farrer
JAMA 287:715-6. 2002