Cerebrospinal Fluid p75 Neurotrophin Receptor Ectodomain Levels Across Clinically Diagnosed Alzheimer's Disease, Late-Life Depression, and Healthy Aging: A Preliminary Cross-Sectional Study.

OBJECTIVE

The p75 neurotrophin receptor ectodomain (p75NTR-ECD) has been implicated in amyloid-β-related neurotoxicity, but cerebrospinal fluid (CSF) levels in late-life depression (LLD) remain uncertain. We compared clinically diagnosed Alzheimer's disease (AD), LLD, and healthy controls (HC) and reassessed exploratory symptom and cognitive associations.

METHODS

CSF p75NTR-ECD was measured in 50 participants (HC, n = 19; LLD, n = 19; AD, n = 12). The primary linear model adjusted for age, sex, and body mass index. Exploratory symptom and cognitive models additionally adjusted for diagnostic group; six p values underwent Benjamini-Hochberg false discovery rate (FDR) correction. Plate and below-calibrator sensitivity analyses were performed.

RESULTS

CSF p75NTR-ECD was higher in HC than in AD (B = 131.2 pg/mL, 95% CI 42.8-219.6, p = 0.005) and higher in LLD than in AD (B = 154.6 pg/mL, 95% CI 68.9-240.3, p < 0.001); HC and LLD did not differ. No symptom or cognitive association remained significant after diagnostic-group adjustment and FDR correction (all q ≥ 0.117). Plate adjustment did not materially change the primary contrasts. Excluding three concentrations below the lowest calibrator preserved the LLD-AD contrast but attenuated the HC-AD contrast.

CONCLUSIONS

CSF p75NTR-ECD showed preliminary differences across clinically defined groups. Because the sample was small, the recruitment site was perfectly confounded with AD versus non-AD status, and diagnoses were not uniformly biomarker-confirmed, the findings do not establish causality, clinical diagnostic utility, or added value beyond established AD biomarkers and require independent multisite replication.