Blood-Based Phosphorylated Tau Isoforms as Emerging Biomarkers for Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive, currently incurable neurodegenerative disorder characterized by cognitive impairment. The neuropathology of AD is defined by two hallmark features: the extracellular deposition of amyloid-β (Aβ) plaques and the intracellular accumulation of neurofibrillary tangles composed of hyperphosphorylated Tau protein. Though cerebrospinal fluid (CSF) testing and imaging techniques such as positron emission tomography (PET) currently serve as diagnostic gold standards, CSF testing is invasive, and the latter is expensive and less accessible. Recent studies document the blood-based phosphorylated Tau (p-Tau) isoforms, particularly p-Tau181, p-Tau217 and p-Tau231, as promising next-generation noninvasive biomarkers for the early diagnosis of AD and disease monitoring. This review summarizes present evidence for clinical utility of blood based p-Tau isoforms, specifically in terms of diagnostic validity, early detection ability, and ability to discriminate AD from other neurodegenerative disorders. Blood-based p-Tau testing holds the possibility to revolutionize AD diagnostic models, with prospects of far-reaching dissemination and early intervention.