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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 cytokines1–5 that are also implicated in Alzheimer disease (AD) pathogenesis6–11. 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.

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Figure 1: E4(+) (▪) and E4(–) () subjects in an HIV-1 cohort were prospectively investigated over six examinations at 6-month intervals.

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The authors thank J. Hartvigsen for help revising the manuscript. This study was supported in part by grants from the National Institute of Neurological Diseases and Stroke (P01-NS26680, R01-NS34234, R01-NS36518), National Institutes of Allergy and Infectious Diseases (AI-25868), the National Center for Research Resources (GCRC-RR00046), the National Institute on Aging (AG07198-09, P20-AG12852-02), the Gun and Bertil Stohne Stiftelsen and the Swedish Medical Research Council.

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Correspondence to Elizabeth H. Corder.

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Corder, E., Robertson, K., Lannfelt, L. et al. HIV-infected subjects with the E4 allele for APOE have excess dementia and peripheral neuropathy. Nat Med 4, 1182–1184 (1998).

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