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

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Abstract

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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Acknowledgments

We are grateful to Dr. Eliezer Masliah (Departments of Pathology and Neurosciences, University of California San Diego) for providing Alzheimer’s disease neocortex sections.

Funding

This research work was supported by the US National Institutes of Health (NIH) grants R56 AG059437 (V. Soontornniyomkij, D. J. Moore, B. Gouaux), R01 MH096648 (A. J. Levine, D. J. Moore, V. Soontornniyomkij, B. Gouaux), U24 MH100928 (D. J. Moore, V. Soontornniyomkij, B. Gouaux), and P50 DA026306 (V. Soontornniyomkij). This publication was made possible from NIH funding through the NIMH and NINDS Institutes by the following grants: Manhattan HIV Brain Bank (MHBB): U24 MH100931, Texas NeuroAIDS Research Center (TNRC): U24 MH100930, National Neurological AIDS Bank (NNAB): U24 MH100929, California NeuroAIDS Tissue Network (CNTN): U24 MH100928, Data Coordinating Center (DCC): U24 MH100925. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the National NeuroAIDS Tissue Consortium (NNTC) or NIH.

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  1. Department of Psychiatry, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA

    Virawudh Soontornniyomkij, David J. Moore, Ben Gouaux & Benchawanna Soontornniyomkij

  2. Departments of Human Genetics, Biomathematics and Biostatistics, David Geffen School of Medicine and Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, USA

    Janet S. Sinsheimer

  3. Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA

    Andrew J. Levine

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  1. Virawudh Soontornniyomkij
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Soontornniyomkij, V., Moore, D.J., Gouaux, B. et al. Associations of regional amyloid-β plaque and phospho-tau pathology with biological factors and neuropsychological functioning among HIV-infected adults. J. Neurovirol. 25, 741–753 (2019). https://doi.org/10.1007/s13365-019-00761-y

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