Journal Article10.1212/01.WNL.0000044340.37138.A9
APOE E4 is a determinant for Alzheimer type pathology in progressive supranuclear palsy.
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TL;DR: Alzheimer type pathology was more frequent in women and older individuals with PSP, and 19 of the 40 patients with PSP with Alzheimer type pathology carried at least one APOE ε4 allele, which was significantly higher in PSP with AD or pathologic aging than in pure PSP.
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Abstract: Objective: To assess demographic and genetic determinants of Alzheimer type pathology in progressive supranuclear palsy (PSP). Methods : From a total of 173 pathologically proven cases of PSP in the Society for PSP Brain Bank, 143 patients (mean age = 74.4 years, ranging from 42 to 98 years) were suitable for genetic and pathologic study. Senile plaques (SPs) and neurofibrillary tangles (NFTs) were counted in five cortical areas, Braak stage was given, and APOE genotype was determined from DNA isolated from frozen brain tissue. The APOE allele frequency in PSP with varying degrees of concomitant Alzheimer type pathology was compared with pure PSP and autopsy controls. The relationship of APOE e4 to quantitative pathologic measures was also assessed. Results: Most patients with PSP (103 cases) had either minimal or no Alzheimer type pathology (Braak stage III or less), but 14 patients had many SPs (>20 per low power field) and a Braak stage of IV or higher consistent with pathologic criteria for AD, and 26 patients had many diffuse plaques with minimal neurofibrillary degeneration (Braak stage III or less) consistent with pathologic aging. Alzheimer type pathology was more frequent in women and older individuals with PSP, and 19 of the 40 patients with PSP with Alzheimer type pathology carried at least one APOE e4 allele. The e4 allele frequency was significantly higher in PSP with AD or pathologic aging than in pure PSP, and APOE e4 correlated with the average maximal density of both neocortical SPs and NFTs. Conclusion: APOE e4 is a risk factor for Alzheimer type pathology in PSP. Alzheimer type pathology is an independent process unrelated to PSP in cases with both types of pathologies.
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Citations
Cognition and Anatomy in Three Variants of Primary Progressive Aphasia
Maria Luisa Gorno-Tempini,Nina F. Dronkers,Katherine P. Rankin,Jennifer M. Ogar,La Phengrasamy,Howard J. Rosen,Julene K. Johnson,Michael W. Weiner,Bruce L. Miller +8 more
TL;DR: Cognitive, genetic, and anatomical features indicate that different PPA clinical variants may correspond to different underlying pathological processes.
Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
TL;DR: Increasing evidence suggests that the effect of APOE*ε4 on AD risk is exerted through inhibition of amyloid-β (Aβ) clearance and promotion of Aβ aggregation, although the relevance of this observation to AD pathogenesis requires further investigation.
ApoE genotype accounts for the vast majority of AD risk and AD pathology.
TL;DR: Evidence is provided that apolipoprotein E (apoE) genotype accounts for the majority of Alzheimer's disease (AD) risk and pathology.
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Progressive Supranuclear Palsy: Pathology and Genetics
TL;DR: Imaging studies suggest that there may be sensitive and specific means to differentiate PSP from other parkinsonian disorders, but identification of a diagnostic biomarker is still elusive.
282
Pesticide exposure and risk of Alzheimer's disease: a systematic review and meta-analysis.
TL;DR: The present meta-analysis suggested a positive association between pesticide exposure and AD, confirming the hypothesis that pesticide exposure is a risk factor for AD.
References
Apolipoprotein E genotype in diverse neurodegenerative disorders.
J. A. Schneider,Marla Gearing,Ronen S. Robbins,William De L’Aune,William De L’Aune,Suzanne S. Mirra +5 more
TL;DR: Preliminary data affirm the need for further study of well‐characterized cases to explore the relationship of ApoE to cytoskeletal pathology and ND and increase the likelihood of an independent association of ϵ4 with amyloid deposition.