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Right arrow Progressive supranuclear palsy
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Neurology 2003;60:240-245
© 2003 American Academy of Neurology

APOE E4 is a determinant for Alzheimer type pathology in progressive supranuclear palsy

Yoshio Tsuboi, MD, Keith A. Josephs, MD, Natalie Cookson, BSc and Dennis W. Dickson, MD

From the Departments of Neurology (Drs. Tsuboi and Josephs) and Pathology (Neuropathology) (Dr. Dickson and N. Cookson), Mayo Clinic, Jacksonville, FL.

Address correspondence and reprint requests to Dr. Dennis W. Dickson, Department of Neuropathology, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224; e-mail: dickson.dennis{at}mayo.edu

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 {epsilon}4 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 {epsilon}4 allele. The {epsilon}4 allele frequency was significantly higher in PSP with AD or pathologic aging than in pure PSP, and APOE {epsilon}4 correlated with the average maximal density of both neocortical SPs and NFTs.

Conclusion: APOE {epsilon}4 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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