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Risk of developing cerebral β-amyloid plaques with post-translational modification among HIV-infected adults.

  • Author(s): Umlauf, Anya
  • Soontornniyomkij, Benchawanna
  • Sundermann, Erin E
  • Gouaux, Ben
  • Ellis, Ronald J
  • Levine, Andrew J
  • Moore, David J
  • Soontornniyomkij, Virawudh
  • et al.
Abstract

OBJECTIVES:Evidence of accelerated brain aging among HIV-infected adults argues for the increased risk of developing cerebral β-amyloid (Aβ) plaques. We compared the frequency of Aβ plaque-bearing cases in our HIV cohort with that in a general cohort reported by Braak et al. (2011). We explored post-translationally modified Aβ forms (N3pE, E22P, phospho-Ser8) in plaques and E22P-Aβ in the postmortem cerebrospinal fluid (CSF) in the HIV cohort. DESIGN:Clinicopathological study of HIV-infected adults. METHODS:To assess frontal Aβ plaque deposition, we conducted immunohistochemistry for generic Aβ (4G8) and three modified Aβ forms. We determined CSF E22P-Aβ levels by ELISA. RESULTS:We found 4G8-Aβ plaques in 29% of 279 HIV-infected cases. Within the age range of 31-70 years, the frequency of 4G8-Aβ plaque-bearing cases was higher in our HIV cohort (n = 273) compared with the general cohort (n = 1110) overall (29.3% vs. 25.8%) and across four age groups by decade (odds ratio 2.35, P < 0.0001). In HIV-infected cases with (n = 37) and without (n = 12) 4G8-Aβ plaques, modified Aβ forms occurred in order: N3pE, E22P, and phospho-Ser8. In CSF assays of HIV-infected cases with (n = 27; 17 focal, 10 widespread) and without (n = 11) 4G8-Aβ plaques, the median E22P-Aβ/Aβ40 ratio was higher among cases with widespread plaques than in cases with focal or absent plaques (P = 0.047). CONCLUSIONS:Our findings suggest HIV-infected adults are at increased risk of developing cerebral Aβ plaques. The occurrence of modified Aβ forms in order suggests the progression stages of Aβ plaque deposition. The potential for E22P-Aβ as a CSF biomarker of cerebral Aβ plaques should be investigated.

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