Use of blood-based biomarker to determine patterns of neurocognitive impairment in people living with HIV

NIH RePORTER · NIH · R03 · $157,500 · view on reporter.nih.gov ↗

Abstract

As the population of people living with HIV (PLWH) ages, they are increasingly at risk of age-related neurocognitive diseases in addition to HIV-related medical co-morbidities such as HIV-associate neurocognitive disorder (HAND). This has resulted in new diagnostic challenges in HIV management. Alzheimer's disease (AD) is the most common underlying cause of neurocognitive disorder in older adults (> 65 years old). Currently available AD diagnostic tools include neuropsychological testing, structural imaging positron emissions tomography (PET) have significant limitations. The ability to differentiate AD from HAND, or the combination of both, early in the disease process is key to ensuring that older PLWH (> 50 years old) receive the appropriate care for neuro-geriatric HIV care. An ideal diagnostic solution would be to demonstrate a potential role for blood-based biomarkers as they could aid in differentiating HAND from AD in older PLWH and overcome many of the barriers posed by other diagnostic modalities. Recent data demonstrated that a novel blood-based biomarker, plasma β amyloid (Aβ) 42/Aβ40 ratio, can accurately determine amyloid PET status in older cognitively normal participants without HIV potentially allowing for screening for early AD. However, nothing is known about this marker in PLWH as it has not yet been measured in this population. Here, we aim to compare plasma levels of Aβ42/Aβ40 in older PLWH to cognitively normal age matched HIV negative controls and symptomatic AD participants and characterize plasma levels of Aβ42/Aβ40 in older PLWH. We hypothesize that plasma Aβ42/Aβ40 ratio will be decreased (worse) in older PLWH compared to HIV-negative controls and that it may predict a pattern of neurocognitive impairment in keeping with AD in PLWH. In addition, we will examine plasma levels of neuro-inflammation and axonal injury in older PLWH and again compare them across groups as well as characterize plasma levels of these markers in older PLWH. We hope to find a blood-based biomarker for AD that can be successfully used in PLWH.

Key facts

NIH application ID
10028243
Project number
1R03AG067995-01
Recipient
WASHINGTON UNIVERSITY
Principal Investigator
Jane A OHalloran
Activity code
R03
Funding institute
NIH
Fiscal year
2020
Award amount
$157,500
Award type
1
Project period
2020-09-30 → 2022-05-31