Alzheimer’s disease (AD) is characterized by progressive cognitive decline and abnormal accumulation of specific proteins in the brain, particularly beta-amyloid and tau. Beta-amyloid peptides, including Aβ42 and Aβ40, are cleavage products of amyloid precursor protein that aggregate to form extracellular plaques, disrupting neural communication. Tau proteins become pathogenic when hyperphosphorylated, including phosphorylated tau isoform ptau181. Blood-based biomarker tests detecting serum levels of Aβ42, Aβ40, Aβ42/Aβ40 ratio, and ptau181 have become clinically available, offering a less invasive and more accessible alternative to cerebrospinal fluid analysis and PET imaging for AD diagnosis and monitoring.
Retrospective analysis of serum Aβ42, Aβ40, Aβ42/Aβ40 ratio, and ptau181 levels was performed on 53 individuals (62.3% female, 69.6 ± 11.4 years) with memory concerns who completed the Neurotrax digital cognitive assessment battery within one year of bloodwork; both of which were performed during routine clinical care. Pearson correlation comparing serum biomarkers and cognitive function was performed using Microsoft Excel. Cognition was evaluated across global cognitive score, memory, attention, language, visuospatial function, motor skills, information processing speed and executive function.
Moderate positive correlations were found between serum Aβ42 and memory (0.44) as well as Aβ40 and global cognitive score (0.36) and memory (0.48). The ratio of Aβ42/Aβ40 and visual spatial ability have a moderate negative correlation (-0.34). Weak positive correlations were found between pTau181, memory (0.25) and executive function (0.27). All other combinations assessed also yielded weak correlations.
Serum Aβ42, Aβ40, Aβ42/Aβ40, and ptau181 biomarkers may provide objective evidence demonstrating need for further neuropsychological evaluation and neurological treatment. While the associations between these biomarkers were generally weak to moderate, additional investigation is needed to detect cognitive vulnerability using these noninvasive biomarkers in larger diverse cohorts.