HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy

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Abstract
HIV produces a chronic viral infection of the central nervous system that elicits chronic glial activation and overexpression of glial cytokines 1–5 that are also implicated in Alzheimer disease (AD) pathogenesis 6–11. A genetic risk factor for AD is the E4 isoform for apolipoprotein E (APOE)12,13. Here we compare the frequency of neurologic symptoms for subjects with and without the E4 isoform (E4(+)and E4(–), respectively) in an HIV cohort14–17. 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.