Predictive value of beta amyloid, phosphorylated Tau, neurofilament light chain, and glial fibrillary acidic protein for depression in Alzheimer's disease.

OBJECTIVES: To investigate differences in biochemical markers and their association with depressive symptoms in patients with Alzheimer's disease (AD) with and without concurrent depression. METHODS: In this retrospective case-control study, 329 AD patients admitted to Beijing Panjiayuan TCM-Western Integrated Hospital between May 2019 and May 2022 were included. Patients were categorized into a comorbid depression group (n=167) and a non-depression group (n=162) based on Cornell Scale for Depression in Dementia (CSDD) scores. Biochemical markers, including β-amyloid proteins (Aβ1-42, Aβ1-40), phosphorylated Tau proteins (p-Tau181, p-Tau217), neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAP), and inflammatory cytokines, were measured and statistically analyzed. RESULTS: High-density lipoprotein cholesterol (HDL-C) was significantly lower in the comorbid depression group (P<0.001). Levels of Aβ1-42 (P=0.012), Aβ1-40 (P=0.006), p-Tau181 (P=0.003), p-Tau217 (P=0.003), NfL (P<0.001), and GFAP (P=0.008) were significantly elevated in the depression group compared to the non-depression group. Additionally, interleukin-10 (P=0.004) and interleukin-6 (P=0.047) levels were higher, while interleukin-1β (P<0.001) was lower in the comorbid depression group. Receiver operating characteristic curve identified HDL-C (area under the curve [AUC]=0.602), p-Tau217 (AUC=0.595), NfL (AUC=0.692), GFAP (AUC=0.580), and IL-1β (AUC=0.600) as significant predictors of depression severity. CONCLUSIONS: Specific biochemical markers, including HDL-C, Aβ42/40, p-Tau217, NfL, GFAP, and IL-1β, are independently associated with depression in AD patients. A combined biomarker model may improve prediction of comorbid depression in AD and provide guidance for personalized treatment.