Plasma phosphorylated tau181 predicts cognitive and functional decline.

Area of Science:

• Biomarkers in Neuroscience
• Neurodegenerative Disease Research
• Clinical Diagnostics

Background:

• Alzheimer's disease (AD) diagnosis relies on clinical assessment and invasive biomarkers.
• Developing accurate, accessible blood-based biomarkers for AD is a critical research area.
• Plasma phosphorylated tau at threonine 181 (p-tau181) is a promising candidate biomarker.

Purpose of the Study:

• To evaluate if plasma p-tau181 can differentiate Alzheimer's disease (AD) pathology from normal cognition (NC).
• To determine if plasma p-tau181 predicts cognitive and functional decline.
• To validate these findings in an independent external cohort.

Main Methods:

• Plasma samples were collected from individuals with neuropathology-confirmed AD, mild cognitive impairment (MCI), AD dementia, and NC.
• Plasma p-tau181 levels were measured using the Quanterix SiMoA HD-X platform.
• Cognitive (MMSE) and functional (CDR) measures were assessed annually; an external cohort (ADNI) was used for validation.

Main Results:

• Plasma p-tau181 accurately distinguished AD pathology from NC (AUC=0.93) with high sensitivity (0.77) and specificity (0.96) at a cut point of 3.44 pg/mL.
• Elevated p-tau181 levels were associated with a faster rate of cognitive decline (MMSE) in AD dementia and MCI.
• Higher p-tau181 levels predicted a shorter time to clinically significant functional decline across all groups and faster conversion to dementia in MCI cases.

Conclusions:

• Plasma p-tau181 is a highly accurate biomarker for differentiating Alzheimer's disease pathology from normal cognition.
• Increased plasma p-tau181 levels are indicative of accelerated cognitive and functional decline.
• These findings support the potential of plasma p-tau181 as a valuable tool in AD diagnosis and prognosis.