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

Nat Med. 1998 Oct;4(10):1182-4. doi: 10.1038/2677.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS Dementia Complex / complications
  • AIDS Dementia Complex / genetics*
  • Adult
  • Alleles
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Cohort Studies
  • Female
  • HIV Infections / complications
  • HIV Infections / genetics*
  • Humans
  • Male
  • Middle Aged
  • Peripheral Nervous System Diseases / complications
  • Peripheral Nervous System Diseases / genetics*
  • Prospective Studies
  • Protein Isoforms


  • Apolipoprotein E4
  • Apolipoproteins E
  • Protein Isoforms