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The Evolving Role of Tau: From Pathology to Precision in Alzheimer’s Diagnosis

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What if one of the most overlooked proteins in the brain turned out to hold the key to understanding—and eventually treating — Alzheimer’s disease?

That question was at the center of a recent Pearson-sponsored podcast series, The Progress Profile: Alzheimer’s Research in Focus. Leading Alzheimer’s researcher Dr. Philip Scheltens joined moderator moderator, John Harrison, Ph.D., CPsychol, CSci, AFBPsS, an associate professor at Alzheimercentrum, AUmc, Amsterdam, to explore how tau has moved from a supporting role in the “amyloid hypothesis” to a central player in diagnosis, imaging, treatment, and precision medicine.

From the Shadows to the Spotlight

Early research focused on the amyloid hypothesis, which proposed that sticky clumps of beta-amyloid protein disrupt cell communication and trigger a cascade of brain damage. Scheltens emphasized that tau soon follows amyloid in this destructive process.

“It’s an extracellular deposit disrupting discussions between cells,” he explained. “Network disruption leads to a cascade that involves tau deposition … and [tau and amyloid deposits together] then lead to neurodegeneration.”

Where amyloid may initiate the disease, tau determines how — and how fast — the symptoms progress.

What Is Tau and Why Does It Matter?

Tau proteins normally help stabilize the internal structure of neurons. In Alzheimer’s disease, tau becomes abnormal and forms tangles inside brain cells that disrupt brain function, contributing to memory and cognitive issues.

Scheltens explained that when tau pathology occurs, it creates episodic memory impairment, executive dysfunction, or language issues, depending on where the tau develops. 

“It is the tau pathology and the location and the amount of subtle pathology that actually gives rise to certain symptoms,” he says. “You can have amyloid in the brain for a long time without notable symptoms.”

Tau as a Biomarker

One of the biggest advances in recent years is the ability to measure tau directly in spinal fluid and even in blood tests. These biomarkers can identify Alzheimer’s pathology years before symptoms emerge.

“Amyloid and tau pathology occurs maybe 10, 15, some say 20 years before the first cognitive complaints occur,” Scheltens noted.

While widespread early testing is not yet recommended, Scheltens explained that tau biomarkers are transforming clinical practice, especially in specialized memory clinics.

Advances in Tau Imaging

Scheltens shared another breakthrough in Alzheimer’s research: Tau PET imaging. The testing allows clinicians to see how tau spreads through the brain in real time; it can show the location of tau and correlate it to the measured cognitive defects.  

“There is a long preclinical phase of Alzheimer’s disease that would lend itself to early detection if we would apply imaging techniques like amyloid PET or … blood-based biomarkers targeting the presence of amyloid and the presence of tau in the earliest phase, perhaps even before patients are complaining about memory or have actually established memory dysfunction,” Scheltens said.

By staging disease progression and pinpointing affected regions, tau imaging is becoming a powerful tool for diagnosis, staging the disease, and monitoring treatment impact.

Tau as a Therapeutic Target

With tau now recognized as central to disease progression, therapies are being developed to slow or block its buildup. These include antibodies, small molecules, and even tau vaccines, Scheltens explained.

While treatments targeting amyloid have produced mixed results, tau offers a new frontier. The hope is that by intervening at the level of tau tangles, future therapies may deliver greater clinical benefit.

Tau and Precision Medicine

In the episode, Scheltens emphasized that the disease process varied among patients, with some experiencing early memory loss while others deal with language or behavioral symptoms. Tau, he said, helps explain this diversity.

By measuring tau biomarkers, clinicians can better classify subtypes of Alzheimer’s, predict disease course, and tailor treatments. This marks a step toward precision medicine, where care is guided by each patient’s unique biology.

Beyond Alzheimer’s: A Wider Role for Tau

Importantly, tau is relevant not only to Alzheimer’s. Other dementias, such as frontotemporal dementia, also involve tau abnormalities, and Scheltens pointed to the urgent need for broader biomarker development.

“Going forward, it’s extremely important that we develop biomarkers for all the different pathologies,” he says. “That will allow us to develop drugs to target them.”

The future of Alzheimer’s disease research will likely expand beyond amyloid and tau, but tau remains the bridge connecting early detection, individualized diagnosis, and targeted therapy.

Episode Takeaways:

  • Tau is central, not secondary: Once overshadowed by amyloid, tau is now recognized as the main driver of cognitive decline in Alzheimer’s.
  • Biomarker revolution: New tau blood tests and CSF assays enable earlier and more accurate diagnosis.
  • Imaging innovation: PET scans reveal how tau spreads in the brain, explaining why symptoms vary among patients.
  • Therapeutic potential: Tau-targeting drugs from antibodies to vaccines are under development.
  • Precision medicine: Tau biomarkers help identify Alzheimer’s subtypes and predict progression, paving the way for personalized care.

Watch Episode 2: “Amyloids and Beyond” of The Progress Profile to learn more about the role of tau in Alzheimer’s disease.