Biomarkers

Background: The identification of biomarkers for Alzheimer's disease (AD) remains a significant challenge, particularly for the clinical severity of the disease. Recent studies have shown that plasma brain-derived-tau (BD-Tau) could be a promising biomarker for the identification of AD-type neurodegeneration. This study aimed to investigate the potential of BD-Tau in differentiating various clinical stages of AD, ranging from cognitively unimpaired AD to severe dementia AD. Additionally, the study intended to examine the association of BD-Tau with clinical severity and elucidate its dynamic behavior throughout the natural course of AD.

Method: Cross-sectional and longitudinal EDTA plasma data, along with clinical information, were utilized from the Pitié-Salpêtrière hospital INSIGHT (cognitively unimpaired individuals with amyloid PET) and SOCRATES cohorts (AD and non-AD symptomatic neurodegenerative disease according to up-to-date international criteria). Plasma BD-Tau was analyzed using the Gothenburg University homebrew Quanterix Simoa immunoassay.

Result: The results revealed that BD-Tau is only elevated in individuals with symptomatic AD, whether the primary or secondary neurodegenerative disease, and not in other neurodegenerative conditions. Additionally, BD-Tau follows the clinical dynamics of AD, as it is only elevated in symptomatic AD patients, while individuals with AD biological changes but no symptoms have normal levels of BD-Tau. BD-Tau levels were also found to be significantly correlated with episodic memory scores and global cognitive performance across a wide range of AD severity. Longitudinal analyses further support BD-Tau's potential as an AD-type neurodegeneration biomarker, as it was found to increase over time only in the symptomatic AD group and not in other groups.

Conclusion: These results support the notion that plasma BD-Tau could be a promising specific biomarker for AD staging, as it follows the AD clinical severity spectrum and is not elevated in asymptomatic amyloidosis.