Plasma biomarkers identify older adults at risk of Alzheimer's disease and related dementias in a real-world population-based cohort

• IntroductionPlasma biomarkers-cost effective, non-invasive indicators of Alzheimer's disease (AD) and related disorders (ADRD)-have largely been studied in clinical research settings. Here, we examined plasma biomarker profiles and their associated factors in a population-based cohort to determine whether they could identify an at-risk group, independently of brain and cerebrospinal fluid biomarkers. MethodsWe measured plasma phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta (A beta)42/40 ratio in 847 participants from a population-based cohort in southwestern Pennsylvania. ResultsK-medoids clustering identified two distinct plasma A beta 42/40 modes, further categorizable into three biomarker profile groups: normal, uncertain, and abnormal. In different groups, plasma p-tau181, NfL, and GFAP were inversely correlated with A beta 42/40, Clinical Dementia Rating, and memory composite score, with the strongest associations in the abnormal group. DiscussionAbnormal plasma A beta 42/40 ratio identified older adult groups with lower memory scores, higher dementia risks, and higher ADRD biomarker levels, with potential implications for population screening. HighlightsPopulation-based plasma biomarker studies are lacking, particularly in cohorts without cerebrospinal fluid or neuroimaging data.In the Monongahela-Youghiogheny Healthy Aging Team study (n = 847), plasma biomarkers associated with worse memory and Clinical Dementia Rating (CDR), apolipoprotein E epsilon 4, and greater age.Plasma amyloid beta (A beta)42/40 ratio levels allowed clustering participants into abnormal, uncertain, and normal groups.Plasma A beta 42/40 correlated differently with neurofilament light chain, glial fibrillary acidic protein, phosphorylated tau181, memory composite, and CDR in each group.Plasma biomarkers can enable relatively affordable and non-invasive community screening for evidence of Alzheimer's disease and related disorders pathophysiology.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Nyckelord

aging

Alzheimer's disease and related disorders

cluster modeling

cognitive impairment

epidemiology

Monongahela-Youghiogheny Healthy

Aging Team (MYHAT)

plasma biomarker

population-based cohort

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