# Cerebrospinal fluid markers of alzheimer’s pathology relate to aMCI among people with HIV

## TL;DR

This study explores how cerebrospinal fluid markers can help distinguish Alzheimer's-related memory issues from other cognitive problems in people with HIV.

## Contribution

The study identifies CSF p-Tau181 as a potential biomarker for aMCI in people with HIV, distinguishing it from HAND.

## Key findings

- CSF p-Tau181 levels were higher in people with HIV who had aMCI compared to those without aMCI.
- The p-Tau181/Aβ42 ratio was elevated in those with an aMCI-like profile but did not reach statistical significance.
- No other biomarkers significantly differed between diagnostic groups.

## Abstract

As people with HIV survive to older ages, they become more at risk for Alzheimer’s disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI). Memory impairment is also common in other neurocognitive disorders (NDs), including HIV-associated neurocognitive disorders (HAND), which makes it a challenge to diagnose aMCI among PWH. Therefore, we assessed the utility of cerebrospinal fluid (CSF) AD pathology markers in distinguishing aMCI from HAND in PWH by investigating how these markers differentially relate to aMCI.

Participants included 74 PWH (Mean age = 48 [SD = 8.5]; 87.4% male, 56.5% White) from the National NeuroHIV Tissue Consortium who consented to a lumbar puncture and had CSF biomarker data for Aβ42, p-Tau181, p-Tau181/Aβ42 ratio, neopterin, and neurofilament light chain (NfL) data, as well as completed a neurocognitive battery. Participants were classified as aMCI using Jak/Bondi criteria (if they had impairment (≥ 1.0 standard deviation [SD] below the mean) on ≥ 2 memory outcomes among learning, delayed recall, and recognition, with at least one recognition impairment required). HAND participants had impairment (≥ 1.0 SD below the mean) in ≥ 2 cognitive domains. HIV disease characteristics and demographic covariates were included in separate linear regression models that examined how individual biomarkers relate to diagnostic status.

Among participants, 43.2% met the criteria for aMCI, 51.3% for HAND, and 34.2% met the criteria for both HAND and aMCI. Greater AD pathology, specifically CSF p-Tau181, was higher in PWH with aMCI compared to PWH without aMCI (F(1,48) = 4.789; p =.034; ηp2 = 0.091). CSF p-Tau181 did not differ by HAND status. While the p-Tau181/Aβ42 ratio was greater among those with an aMCI-like profile among PWH, it did not reach a statistically significant difference. No other biomarker significantly differed by group status.

Results suggest CSF p-Tau181 is indicative of an aMCI-like cognitive profile among PWH, and may be a biologically distinct subgroup of PWH with HAND. More precise diagnosis of aMCI will allow earlier planning; however, more long-term studies are needed to determine the direction of the current results.