Neuronal accumulation of hyperphosphorylated tau protein predicts stable memory impairment in people living with HIV.

TitleNeuronal accumulation of hyperphosphorylated tau protein predicts stable memory impairment in people living with HIV.
Publication TypeJournal Article
Year of Publication2023
AuthorsGonzalez, J, Wilson, A, Byrd, D, Cortes, EP, Crary, JF, Morgello, S
Date Published2023 Jul 01
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Cognitive Dysfunction, HIV Infections, Humans, Memory Disorders, Memory, Short-Term, Middle Aged, Positron-Emission Tomography, tau Proteins

OBJECTIVES: As lifespans increase in people with HIV (PWH), there is concern that age-related neurodegenerative disorders may contribute to cognitive decline. We asked whether brain accumulation of Alzheimer's disease (AD)-associated proteins amyloid-beta (Aβ) and hyperphosphorylated tau (p-tau) predicted cognitive performance in middle-aged PWH.METHODS: In a prospectively followed, cognitively-characterized autopsy sample of 135 PWH, we used immunohistochemistry to assess Aβ plaques and neuronal p-tau in medial temporal and lateral frontal lobes. These pathologies were tested for associations with cognitive performance in seven domains: motor, speed of information processing, working memory, memory encoding, memory retrieval, verbal fluency, and abstraction/executive function. Univariate and multivariate analyses accounting for HIV-associated variables, reading level, and comorbidities were conducted. Longitudinal trajectories of memory functions were evaluated in 60 individuals with a median follow-up of 6.0 years.RESULTS: In this population with mean age 51.4 ± 0.9 years, 58% displayed neuronal p-tau and 29% Aβ plaques. Neuronal p-tau, but not Aβ, predicted worse memory encoding and retrieval, but not other cognitive functions. With an ordinal hierarchy of neuronal p-tau locations (entorhinal, hippocampal, neocortical), decreased memory performance correlated with neocortical distribution. Memory function trajectories could not be distinguished between individuals with and without neuronal p-tau, and over 80% of the sample showed no change over time.CONCLUSION: In this middle-aged sample, neuronal p-tau accumulation contributes to memory deficits, but is not associated with accelerated decline in function over time. In the absence of AD-like deterioration, other etiologies for neuronal p-tau in cognitively impaired PWH must be considered.

Alternate JournalAIDS
PubMed ID36988209
PubMed Central IDPMC10539475
Grant ListU24 MH100931 / MH / NIMH NIH HHS / United States
R01 NS108801 / NS / NINDS NIH HHS / United States
R01 NS095252 / NS / NINDS NIH HHS / United States
RF1 AG060961 / AG / NIA NIH HHS / United States
R01 AG054008 / AG / NIA NIH HHS / United States