Plasma Aβ42/Aβ40 Ratios in Older People With Human Immunodeficiency Virus

Abstract

Background As people with HIV (PWH) age, it remains unclear whether they are at higher risk for age-related neurodegenerative disorders, e.g., Alzheimer disease (AD), and if so, how to differentiate HIV-associated neurocognitive impairment from AD. We examined a clinically-available blood biomarker test for AD (plasma Aβ42/Aβ40 ratio), in cognitively-normal (CN) or cognitively-impaired (CI) PWH and people without HIV (PWoH) who were CN or with symptomatic AD. Methods 66 PWH (age >40 years) (HIV RNA <50 copies/mL) and 195 PWoH provided blood samples, magnetic resonance imaging (MRI), and completed a neuropsychological battery or Clinical Dementia Rating scale (CDR). Participants were categorized by impairment (PWH_CN n = 43; PWH_CI n = 23; PWoH_CN n = 138; PWoH_AD n = 57). Plasma Aβ42 and Aβ40 concentrations were obtained using a liquid chromatography-tandem mass spectrometry method to calculate the PrecivityAD® Amyloid Probability Score (APS). The APS incorporates age and apolipoprotein E proteotype into a risk score for brain amyloidosis. Plasma Aβ42/Aβ40 and APS were compared between groups and assessed for relationships with hippocampal volumes or cognition and HIV clinical characteristics (PWH only). Results The plasma Aβ42/Aβ40 ratio was significantly lower, and APS higher, in PWoH_AD compared to other groups. A lower Aβ42/Aβ40 ratio and higher APS was associated with smaller hippocampal volumes for PWoH_AD. The Aβ42/Aβ40 ratio and APS were not associated with cognition or HIV clinical measures for PWH. Conclusions The plasma Aβ42/Aβ40 ratio can serve as a screening tool for AD and may help differentiate effects of HIV from AD within PWH, but larger studies with older PWH are needed.

CSF Extracellular Vesicle Aβ42 and Tau/Aβ42 Ratio Are Associated with Cognitive Impairment in Older People with HIV

“…Moreover, soluble Aβ42 and Tau/Aβ42 did not correlate with corresponding CSF EV-associated forms. Consistent with these findings, some studies reported no significant difference in Aβ deposition according to HIV serostatus or HAND stage [58,59], while others reported no significant difference in CSF Aβ peptides and p-Tau concentrations between groups stratified by HIV or HAND [26,60]. Unexpectedly, we observed higher CSF Aβ42 levels in PWH compared with HIV− controls; the explanation for this finding remains unclear and warrants further study.…”

“…An increased CSF Tau/Aβ42 ratio is a biomarker associated with risk of aMCI and AD; increased CSF Tau reflects its release from degenerating neurons while decreased CSF Aβ42 reflects higher amyloid deposition in the brain [ 21 , 22 , 23 , 24 ]. Most studies of aMCI/AD-related biomarkers according to HIV serostatus have not detected a significant increase among PWH compared to the general population [ 11 , 20 , 25 , 26 , 27 ]. Moreover, early neuroinflammation in PWH might have protective effects against Aβ and Tau deposition in the brain [ 28 ].…”

Nucleoside Reverse Transcriptase Inhibitor Exposure Is Associated with Lower Alzheimer’s Disease Risk: A Retrospective Cohort Proof-of-Concept Study

“…The implementation of cART changed the clinical definition of HAND to a far milder and generally manageable entity, which notably is characterized as reversible and, therefore, fundamentally different from the relentless and progressive nature of AD [ 44 , 45 , 46 , 47 ]. At least some biomarkers observed in cognitively impaired patients with HIV are distinct from AD (e.g., Aβ42/Aβ40 ratios are not reduced in HIV, contrasting with AD) [ 48 ]. Moreover, neuropathological differences have emerged between HAND and AD, including differences in amyloid plaque morphology, which is typically diffuse in HAND, contrasting with AD, which is characterized by dense-core plaques [ 49 ] and where diffuse plaques are considered benign lesions [ 50 , 51 ].…”

Plasma Biomarkers of Alzheimer Disease in Women With and Without HIV

“…We observed no association of NP with the Aβ42-to-Aβ40 ratio, which has been associated with an increased incidence of AD in HIV-uninfected aging individuals . However, no association of plasma Aβ42-to-Aβ40 ratio in people aged older than 40 years with AD and without HIV compared with similar-aged PLWH who were cognitively normal or who had AD was also reported …”

“… 9 However, no association of plasma Aβ42-to-Aβ40 ratio in people aged older than 40 years with AD and without HIV compared with similar-aged PLWH who were cognitively normal or who had AD was also reported. 41 …”