Plasma A beta 42/A beta 40 Ratios in Older People Living With Human Immunodeficiency Virus

The plasma amyloid-beta (A beta) 42/A beta 40 ratio, a blood-based biomarker for brain amyloid in Alzheimer disease, is not abnormal in older cognitively normal or cognitively impaired people with human immunodeficiency virus (HIV), compared with similarly aged, cognitively normal people without HIV. Background As people with human immunodeficiency virus (HIV) (PWH) age, it remains unclear whether they are at higher risk for age-related neurodegenerative disorders-for example, 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 amyloid-beta [A beta] 42/A beta 40 ratio) in PWH who were cognitively normal (PWH_CN) or cognitively impaired (PWH_CI) and people without HIV (PWoH) who were cognitively normal (PWoH_CN) or had symptomatic AD (PWoH_Ad). Methods A total of 66 PWH (age >40 years) (HIV RNA <50 copies/mL) and 195 PWoH provided blood samples, underwent magnetic resonance imaging, and completed a neuropsychological battery or clinical dementia rating scale. Participants were categorized by impairment (PWH_CN, n = 43; PWH_CI, n = 23; PWoH_CN, n = 138; PWoH_Ad, n = 57). Plasma A beta 42 and A beta 40 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 A beta 42/A beta 40 ratios and APSs were compared between groups and assessed for relationships with hippocampal volumes or cognition and HIV clinical characteristics (PWH only). Results The plasma A beta 42/A beta 40 ratio was significantly lower, and the APS higher, in PWoH_AD than in other groups. A lower A beta 42/A beta 40 ratio and higher APS was associated with smaller hippocampal volumes for PWoH_AD. The A beta 42/A beta 40 ratio and APS were not associated with cognition or HIV clinical measures for PWH. Conclusions The plasma A beta 42/A beta 40 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.