Exploring the effect of APOE ε4 on biomarkers of neurodegeneration in Alzheimer's disease

Abstract

Background and aims: This study aims to assess the association between APOE genotype and biomarkers of neurodegeneration in Alzheimer's disease (AD). Methods: We performed a retrospective observational study at the University Hospital “P. Giaccone” in Palermo, Italy. We enrolled patients with cognitive decline, including AD. For each patient, we measured amyloid beta (Aβ)42, Aβ40, tau protein phosphorylated at threonine 181 (pTau), total tau (tTau), neurogranin, alpha-synuclein, and neurofilament light chain (NfL) in cerebrospinal fluid (CSF). Results: The study population consisted of 194 patients (123 AD and 71 non-AD). AD patients have significantly lower Aβ42 levels and Aβ42/40 ratio and higher pTau, tTau, and NfLs levels than non-AD patients. In AD patients, the APOEε4 allele is associated with a significantly lower Aβ42/40 ratio and higher levels of pTau, tTau, neurogranin, and alpha-synuclein. This association is not observed in non-AD patients. Conclusions: This study provides evidence of the significant impact of the APOE ε4 allele on neurodegenerative biomarkers in AD patients, highlighting its role in exacerbating amyloid and tau pathology as well as synaptic degeneration.