CSF Aβ40 levels do not correlate with the clinical manifestations of Alzheimer's Disease.

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 aims to investigate the clinical and prognostic significance of Aβ40 CSF levels. Methods A retrospective cohort of 76 patients diagnosed with AD using decreased Aβ42/Aβ40 ratio were subclassified into hyposecretors (Aβ40<7755 pg/ml), normosecretors (Aβ40 7755-16715 pg/ml), and hypersecretors (Aβ40>16715pg/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 5870.500 pg/ml, interquartile range (IQR) 1431), normosecretors (n=47, median Aβ40 10817 pg/ml, IQR 3622), and hypersecretors (n=7, 19767 pg/ml, IQR 3088). 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.