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(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 cohort(14-17). 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.