CSF Aβ40 Levels Do Not Correlate with the Clinical Manifestations of Alzheimer’s Disease

Abstract

Introduction: Cerebrospinal fluid (CSF) biomarker quantification provides physicians with a reliable diagnosis of Alzheimer’s disease (AD). However, the relationship between their concentration and disease course has not been clearly elucidated. This work aimed to investigate the clinical and prognostic significance of Aβ₄₀ CSF levels. Methods: A retrospective cohort of 76 patients diagnosed with AD using a decreased Aβ₄₂/Aβ₄₀ ratio was subclassified into hyposecretors (Aβ₄₀ <7,755 pg/mL), normosecretors (Aβ₄₀ 7,755–16,715 pg/mL), and hypersecretors (Aβ₄₀ >16,715 pg/mL). Potential differences in AD phenotype, Montreal Cognitive Assessment (MoCA) scores, and Global Deterioration Scale (GDS) stages were assessed. Correlation tests for biomarker concentrations were also performed. Results: Participants were classified as hyposecretors (n = 22, median Aβ₄₀ 5,870.500 pg/mL, interquartile range [IQR] 1,431), normosecretors (n = 47, median Aβ₄₀ 10,817 pg/mL, IQR 3,622), and hypersecretors (n = 7, 19,767 pg/mL, IQR 3,088). The distribution of positive phosphorylated Tau (p-Tau) varied significantly between subgroups and was more common in the normo- and hypersecretor categories (p = 0.003). Aβ₄₀ and p-Tau concentrations correlated positively (ρ = 0.605, p < 0.001). No significant differences were found among subgroups regarding age, initial MoCA score, initial GDS stage, progression to the dementia stage, or changes in the MoCA score. Conclusion: In this study, we found no significant differences in clinical symptoms or disease progression in AD patients according to their CSF Aβ₄₀ concentration. Aβ₄₀ was positively correlated with p-Tau and total Tau concentrations, supporting their potential interaction in AD pathophysiology.