Associations of regional amyloid-β plaque and phospho-tau pathology with biological factors and neuropsychological functioning among HIV-infected adults.

Publisher: Springer Country of Publication: United States NLM ID: 9508123 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-2443 (Electronic) Linking ISSN: 13550284 NLM ISO Abbreviation: J Neurovirol Subsets: MEDLINE

Publication: 2011- : New York : Springer
Original Publication: Houndmills, Basingstoke, Hampshire ; New York, NY : Stockton Press, c1995-

Cognition*; Brain/*pathology ; HIV Infections/*pathology ; Neurofibrillary Tangles/*pathology ; Plaque, Amyloid/*pathology; Adult ; Aged ; Amyloid beta-Peptides/metabolism ; Female ; HIV Infections/complications ; HIV-1 ; Humans ; Male ; Middle Aged ; Neuropsychological Tests ; tau Proteins/metabolism

With increasing age, the general population is increasingly vulnerable to the development of cerebral amyloid-β (Aβ) plaque and neuronal phospho-tau (p-tau) pathology. In HIV disease, prior studies of these neuropathologic changes were relatively limited. Here, we characterized Aβ plaques and p-tau lesions by immunohistochemistry in relevant brain regions (prefrontal neocortex, putamen, basal-temporal neocortex, and hippocampus) of HIV-infected adults. We used multivariable logistic regression to predict regional Aβ plaque or p-tau pathology based on demographic factors, apolipoprotein E (APOE) genotypes, HIV disease-related factors, and regional gliosis. We used multiple linear regression to predict T-scores in neuropsychological domains based on regional Aβ plaque or p-tau pathology. We found that APOE ε4 alleles, older age, and higher plasma HIV-1 RNA predicted prefrontal Aβ plaques (odds ratio (OR) 5.306, 1.045, and 0.699, respectively, n = 168). Older age predicted putamen Aβ plaques (OR 1.064, n = 171). APOE ε4 alleles, hepatitis C virus seropositivity, and higher plasma HIV-1 RNA predicted hippocampus Aβ plaques (OR 6.779, 6.138, and 0.589, respectively, n = 56). The p-tau lesions were sparse in the vast majority of affected cases. Lifetime substance use disorder and higher plasma HIV-1 RNA predicted putamen p-tau lesions (OR 0.278 and 0.638, respectively, n = 67). Older age and gliosis predicted hippocampus p-tau lesions (OR 1.128 and 0.592, respectively, n = 59). Prefrontal Aβ plaques predicted lower speed of information processing (n = 159) and putamen Aβ plaques predicted lower levels of attention and working memory (n = 88). Regional p-tau lesions were not significantly predictive of any neuropsychological domains. In conclusion, Aβ plaque or p-tau pathology in different brain regions was predicted by different sets of biological factors. Aβ plaques in prefrontal neocortex and putamen predicted poorer functioning in cognitive domains relevant to these brain regions. The absence of significant impact of regional p-tau lesions on neuropsychological functioning might be explained by the subthreshold burden of p-tau lesions.

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U24 MH100929 United States MH NIMH NIH HHS; U24 MH100925 United States MH NIMH NIH HHS; P50 DA026306 United States DA NIDA NIH HHS; U24 MH100931 United States MH NIMH NIH HHS; U24 MH100928 United States MH NIMH NIH HHS; R01 MH096648 United States MH NIMH NIH HHS; P30 MH062512 United States MH NIMH NIH HHS; U24 MH100930 United States MH NIMH NIH HHS; R56 AG059437 United States AG NIA NIH HHS

Keywords: Amyloidosis; Astrogliosis; Gliosis; Microgliosis; Neurodegeneration; Tauopathy

0 (Amyloid beta-Peptides)
0 (tau Proteins)

Date Created: 20190531 Date Completed: 20201021 Latest Revision: 20241127

20241202

PMC6883131

10.1007/s13365-019-00761-y

31144289