Plasma-derived biomarkers of Alzheimer's disease and neuropsychiatric symptoms: A community-based study

Introduction: We examined associations between plasma-derived biomarkers of Alzheimer's disease (AD) and neuropsychiatric symptoms (NPS) in community-dwelling older adults.

Methods: Cross-sectional study involving 1005 persons ≥50 years of age (mean 74 years, 564 male, 118 cognitively impaired), who completed plasma-derived biomarker (amyloid beta 42 [Aβ42]/Aβ40, phosphorylated tau 181 [p-tau181], p-tau217, total tau [t-tau], neurofilament light [NfL]), and NPS assessment.

Results: P-tau181 (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.41-3.00, p < 0.001), p-tau217 (OR 1.70, 95% CI 1.10-2.61, p = 0.016), and t-tau (OR 1.44, 95% CI 1.08-1.92, p = 0.012) were associated with appetite change. We also found that p-tau181 and p-tau217 were associated with increased symptoms of agitation (OR 1.93, 95% CI 1.20-3.11, p = 0.007 and OR 2.04, 95% CI 1.21-3.42, p = 0.007, respectively), and disinhibition (OR 2.39, 95% CI 1.45-3.93, p = 0.001 and OR 2.30, 95% CI 1.33-3.98, p = 0.003, respectively). Aβ42/Aβ40 and NfL were not associated with NPS.

Conclusion: Higher plasma-derived p-tau181 and p-tau217 levels are associated with increased symptoms of appetite change, agitation, and disinhibition. These findings may support the validity of plasma tau biomarkers for predicting behavioral symptoms that often accompany cognitive impairment.

Highlights: We studied 1005 community-dwelling persons aged ≥ 50 yearsHigher plasma tau levels are associated with increased neuropsychiatric symptomsAβ42/Aβ40 and NfL are not associated with neuropsychiatric symptomsClinicians should treat neuropsychiatric symptoms in persons with high plasma-derived tau.