Tau Changes Revealed Over Long Lead-up to Alzheimer’s Disease

What: Scientists describe how the protein tau is modified over four decades as Alzheimer’s develops and progresses.

Where: Barthélemy NR, et al, “A Soluble Phosphorylated Tau Signature Links Tau, Amyloid and the Evolution of Stages of Dominantly Inherited Alzheimer's Disease,” Nature Medicine, 2020

BrightFocus Connection: This project was supported by an Alzheimer’s Disease Research grant to senior author Randall Bateman, MD, Washington University School of Medicine.

Randall Bateman, MD

Why It Is Important: In Alzheimer’s disease (AD), scientists believe that changes to tau, beta-amyloid (Aβ), and other brain proteins cause damage over time and eventually lead to memory loss and other changes to cognition and behavior, culminating in dementia and death. Until the past decade, tau has not been as well studied as Aβ. Now scientists involved with the Dominantly Inherited Alzheimer’s Network (DIAN), including BrightFocus-funded Dr. Bateman, have identified patterns of changes in tau occurring over four decades of disease progression which follow distinct trajectories over time. These changes are uniquely associated with structural, metabolic, neurodegenerative and clinical markers of AD. 

To reach these findings, DIAN investigators studied tau molecules in cerebrospinal fluid (CSF) samples collected from individuals with the early-onset, genetically linked types of AD (referred to as dominantly inherited AD). The results show that disease-associated forms of tau emerge as early as when Aβ starts to accumulate, decades before dementia symptoms begin. Ultimately these changes cause tau molecules to form “fibrils,” or slender threads that gather as tau tangles inside neurons, blocking the cellular transport system and disrupting brain signals.

Not long after these DIAN findings were published by Dr. Bateman and colleagues, other researchers described similar changes in tau arising early in sporadic (eg, non-inherited) forms of AD, an estimated 21 years before symptom. Together these findings provide evidence that tau changes may be an important biomarker of early AD, as well as a target of future treatments.