Development of a plasma biomarker diagnostic model as a screening strategy for Alzheimer's disease in older inpatients

Abstract Neural proteins in the bloodstream have emerged as promising biomarkers for diagnosing Alzheimer's disease (AD). However, their applicability in older individuals and those with multiple co‐existing health conditions remains under‐investigated. This study evaluated the diagnostic potential of blood‐based neuro‐markers in participants over 75 years old using an ultra‐sensitive single molecule array. We recruited 108 Chinese inpatients with an average age of 92 years, including 30 diagnosed with AD, 46 diagnosed with dementia not caused by AD, and 32 without dementia. Plasma concentrations of amyloid β‐40 (Aβ40), amyloid β‐42 (Aβ42), tau phosphorylated at threonine 181 (p‐tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) in plasma were quantified along with the Aβ42/Aβ40 ratio. Associations between these biomarkers and clinical characteristics (comorbidities and physiological indicators) were examined. Diagnostic models were developed using binary logistic regression based on these neuro‐markers. Among the six neuro‐markers, p‐tau181 exhibited the highest discriminatory power for AD identification, with an area under the curve (AUC) of 0.7731 (95% CI: 0.6493–0.8969). A model combining p‐tau181, GFAP, and age achieved an AUC of 0.8654 (95% CI: 0.7762–0.9546), with 75.9% sensitivity and 80.6% specificity in distinguishing AD from individuals without dementia. These findings suggest that plasma biomarkers of neurodegeneration, particularly p‐tau181, may hold significant promise as diagnostic tools for AD, even among older patients. The simplified diagnostic model based on plasma neuro‐markers offers a feasible approach for AD screening in both clinical and community settings.