TOPLINE:

Plasma phosphorylated tau 181 (p-tau181) could not only serve as a reliable biomarker for diagnosing Alzheimer's disease (AD) progression, but it could also identify those who were at risk of converting to AD dementia and worsening of cognition over time since the earliest stage of the disease.

METHODOLOGY:

• Researchers conducted a longitudinal study to determine whether plasma p-tau181 could identify patients with mild cognitive impairment and subjective cognitive decline who would convert to AD dementia.
• They enrolled 163 participants (50 with subjective cognitive decline, 70 with mild cognitive impairment, and 43 with AD dementia) between 2018 and 2024 who were evaluated for plasma p-tau181 levels using the Simoa assay.
• Patients were classified according to the Revised Criteria of Alzheimer's Association Workgroup as those who were Core1 positive in case of abnormality on at least one of specific Core1 biomarkers and those who were Core1 negative in case of normal Core1 biomarkers.

TAKEAWAY:

• At a cutoff value of 2.25 pg/mL, plasma p-tau181 showed good accuracy (85.90%), sensitivity (92.78%), and specificity (74.58%) in distinguishing between patients who were Core1 positive and Core1 negative.
• Patients with positive p-tau181 levels showed a higher risk for conversion to AD dementia than those with negative p-tau181 levels (hazard ratio, 11.65; P = .018).
• In patients with subjective cognitive decline and positive p-tau181 levels, 15 Rey Verbal Learning Test Delayed Recall scores declined from 10.54 at baseline to 8.30 after 2 years (P = .012) and Rey-Osterrieth complex figure recall scores declined from 19.64 at baseline to 16.76 after 2 years (P = .009), indicating worsening long-term memory performance.

IN PRACTICE:

"This finding underscores the importance of prognostic biomarkers in distinguishing patients at higher risk of developing AD dementia, enabling clinicians to intervene at a stage where treatments might be most effective and helping researchers select appropriate candidates for clinical trials aimed at delaying or preventing disease progression," the authors wrote.

SOURCE:

This study was led by Giulia Giacomucci, Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy. It was published online on September 10, 2025, in Annals of Clinical and Translational Neurology.

LIMITATIONS:

Renal function was evaluated only dichotomously for the presence or absence of renal failure rather than using as a continuous variable like creatinine levels. Study results may have limited generalisability due to the absence of cognitively unimpaired control individuals and a small sample size.

DISCLOSURES:

This study was supported by the Tuscany Region and European Union (EU) — Next Generation EU and Investment Partenariato Esteso PE8 — Project Age-It: "Ageing Well in an Ageing Society." The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.