Phosphorylated tau in Alzheimer's disease

Area of Science:

• Neuroscience
• Biomarker Discovery
• Alzheimer's Disease Research

Background:

• Current Alzheimer's disease (AD) diagnosis relies on invasive cerebrospinal fluid biomarkers or costly PET scans.
• Plasma phosphorylated tau proteins (p-tau) are emerging as less invasive blood-based biomarkers for AD.
• This review focuses on plasma tau phosphorylated at threonine 181 (p-tau181), threonine 217 (p-tau217), and threonine 231 (p-tau231).

Approach:

• Systematic review conducted following PRISMA guidelines.
• Evaluated the diagnostic and prognostic utility of plasma p-tau181, p-tau217, and p-tau231 in Alzheimer's disease.
• Assessed biomarker correlation with amyloid-beta (Aβ) and tau pathology, disease severity, and cognitive decline.

Key Points:

• All evaluated p-tau isoforms increase with amyloid-beta accumulation and distinguish preclinical AD from healthy individuals.
• P-tau231 elevation precedes p-tau181 and p-tau217; p-tau217 shows the largest increase in advanced AD stages.
• Plasma p-tau isoforms correlate with neuroimaging findings, cognitive decline, and differentiate AD from non-AD neurodegenerative diseases.

Conclusions:

• Plasma p-tau biomarkers (p-tau181, p-tau217, p-tau231) are informative for diagnosing Alzheimer's disease across its continuum.
• These biomarkers reflect underlying AD pathology, disease progression, and brain structural changes.
• Further research is needed to standardize assays and establish clinical cut-points for widespread adoption.