HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy.
HIV produces a chronic viral infection of the central nervous system that elicits chronic glial activation and overexpression of glial cytokines that are also implicated in Alzheimer disease (AD) pathogenesis. A genetic risk factor for AD is the E4 isoform for apolipoprotein E (APOE). Here we compare the frequency of neurologic symptoms for subjects with and without the E4 isoform (E4(+)and E4(-), respectively) in an HIV cohort. Compared with E4(-) subjects, twice as many E4(+) subjects were demented (30% compared with 15%) or had peripheral neuropathy (70% compared with 39%) at least once, and they had threefold more symptomatic examinations (13% compared with 3% and 42% compared with 14%, respectively)(P < 0.0001). Thus, neurologic symptoms for HIV-infection and AD are linked through an etiologic risk factor. Long-term survivors of HIV infection with E4 may be at high risk for AD; conversely, gene-viral interactions may speed AD pathogenesis.
Corder
E H
EH
Genetic Epidemiology, Odense University, Denmark. beth@cds.duke.edu
Robertson
K
K
Lannfelt
L
L
Bogdanovic
N
N
Eggertsen
G
G
Wilkins
J
J
Hall
C
C
D015526:AIDS Dementia Complex / Q000150:complications / Q000235:genetics*; D000328:Adult; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics*; D011446:Prospective Studies; D020033:Protein Isoforms
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D020033:Protein Isoforms