Practical NeurologyStudy from CTAD 2023 Compares Sensitivity of 4 Blood-Based Biomarkers for Preclinical Alzheimer Disease

P-Tau217: A Promising Biomarker for Preclinical Alzheimer’s Disease

A recent study presented at the 16th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference has shed light on the potential of blood-based biomarkers in predicting Alzheimer’s disease (AD) during its preclinical stages.

Study Design

• The study compared the sensitivity of four biomarkers: amyloid beta (Aβ) 40/42 ratio, plasma phosphorylated tau at threonine 181 (p-tau181), p-tau217, and neurofilament light chain (NfL).
• Participants were cognitively healthy adults aged 55-80 years (N=98), with mean Montreal Cognitive Assessment (MoCA) general cognition scores of 27 (SD, 1.7).
• The study divided participants into low-risk (LR, n=43) and high-risk (HR, n=55) groups. LR participants were APOE ε4 negative, had no family histories for AD, and no subjective memory impairment (SMI). HR subjects carried at least one apolipoprotein E ε4 (APOE ε4) allele, had a family history for AD, and SMI1.

Key Findings

• P-tau217 was associated with both high-risk for developing AD and elevated neocortical amyloidosis.
• The only difference between LR and HR participants was observed for p-tau217 (HR > LR, P =.03).
• In a subgroup of 25 participants who received a Florbetapen amyloid PET scan, differences in elevated versus non-elevated neocortical amyloidosis were observed for the Aβ 40/42 ratio (HR < LR, P =.03) and p-tau217 (HR > LR, P =.00005), with a greater between-group difference for p-tau217 (AUC=0.850).

According to an article from Neurology, there are two major biomarkers for Alzheimer disease: amyloid-beta peptide (Aβ) and phosphorylated-tau protein (p-tau). Research has shown that by measuring both types and comparing them, the testing accuracy is higher than when measuring either one alone.

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