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Alzheimer's Disease: Overview

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Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...

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In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein

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Published on: January 2, 2015

Sex Differences in P-Tau217, Tau Aggregation, and Cognitive Decline.

Gillian T Coughlan^1,2, Valentin Ourry³, Diana Townsend¹

¹Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.

|February 16, 2026

Summary

Women show increased tau accumulation and cognitive decline with higher amyloid-beta levels, particularly when soluble phosphorylated tau 217 (p-tau217) is present. This suggests a sex-specific Alzheimer's disease progression influenced by early biomarkers.

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Last Updated: Feb 17, 2026

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Published on: May 28, 2017

Area of Science:

Neuroscience
Biomarkers
Alzheimer's Disease Research

Background:

Women with high amyloid-beta (Aβ) exhibit greater insoluble tau burden than men.
The role of soluble phosphorylated tau (p-tau) in this sex difference is unclear.
p-tau is an early biomarker for Alzheimer's disease (AD).

Purpose of the Study:

To investigate if sex and aggregated Aβ synergistically predict plasma p-tau217 levels.
To determine if p-tau217 levels predict tau aggregation and cognitive decline in a sex-specific manner.

Main Methods:

Longitudinal analysis of 1292 participants (63.6% women) from 5 cohorts.
Assessed sex, tau PET imaging, and plasma p-tau217 levels at baseline.
Used linear and mixed-effects models to analyze interactions and longitudinal changes.

Main Results:

Women showed significantly higher baseline p-tau217 at higher aggregated Aβ levels compared to men.
Sex and p-tau217 interactions were significant across multiple tau PET regions and longitudinally.
Women with higher p-tau217 levels exhibited greater tau deposition and faster cognitive decline than men.

Conclusions:

Women exhibit a differential tau response to Aβ, potentially linked to p-tau secretion.
These findings highlight sex-specific pathways in preclinical Alzheimer's disease.
Results have implications for developing targeted therapeutics and diagnostics for AD.