Two Alzheimer's Studies Published Nov. 4: Faster Tau Spread in Younger Patients, Brain-Activity Risk Score in Healthy Adults

Two new Alzheimer's papers, both published Nov. 4, point at the same target from opposite ends of the disease. One explains why Alzheimer's hits some younger patients harder. The other tries to spot the risk before memory loss starts.

Neither study tested a treatment.

Why early-onset Alzheimer's moves faster

People whose symptoms begin before age 65 make up about 5% of all Alzheimer's patients. They often decline faster than older patients. A UCSF-led study in Science Translational Medicine looked at tau, the protein that forms tangles inside brain cells, to find out why.

Researchers analyzed tau PET scans from 390 people with early-onset Alzheimer's in the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS). Their average age was 59. They compared them with 211 late-onset patients from the Alzheimer's Disease Neuroimaging Initiative, average age 78.

All participants had amyloid buildup and either mild cognitive impairment or mild dementia.

The younger group started with substantially higher tau across multiple brain regions. That held even after researchers adjusted for cognitive impairment and amyloid burden. The tau was also spread more widely across the cortex.

A subset got repeat scans over an average of two to three years. In those, tau accumulated at more than twice the rate in the younger patients, according to UCSF. Modeling suggested late-onset patients needed more than five additional years to reach comparable tau levels.

Tau burden also tracked more closely with poor scores on memory and daily-function tests in the younger group. That suggests tau may drive symptoms more directly there.

"Younger patients can already have substantial tau pathology when symptoms are still mild, and the faster accumulation we observed suggests that further delays may be particularly consequential in this group," said lead author Konstantinos Chiotis, now an assistant professor at the Karolinska Institutet in Stockholm.

The patterns also line up with how the disease presents. One in five early-onset patients had a non-memory-dominant form. Among late-onset patients with documented presentations, more than 99% had a memory-dominant form.

Co-senior author Renaud La Joie of UCSF described what that looks like: trouble interpreting what they see despite a normal eye exam, trouble judging distances or reading, word-retrieval problems, and struggles with planning and attention.

Chiotis added a caution. Individual progression varies, he said, and cannot be predicted from the group averages in the study.

A brain-activity score for people with no symptoms

The second paper, from Stanford Medicine, appeared in Science Advances. Researchers first studied resting brain activity in adults 75 and older at two extremes: those diagnosed with Alzheimer's and "super agers," whose memory matches people decades younger.

From those groups they trained a machine-learning model on how brain regions communicate. The result is the Aging-Related Connectome (ARC) signature.

They then applied it to adults aged 55 to 70 with no cognitive decline. The more Alzheimer's-like a person's brain activity, the more likely they were to decline, develop amyloid plaques and be diagnosed within the next 12 years. The more super-ager-like, the more likely they were to avoid those outcomes.

Stanford says the score predicted cognitive decline better than demographics, amyloid and tau biomarkers, and genetics. Lead author Kanhao (Alex) Zhao framed it more modestly: "Our model shows comparable or better prediction ability, and it can do so at an earlier time point." Combining the score with existing biomarkers improves prediction further, he said.

Senior author Yu Zhang, an assistant professor of psychiatry and behavioral sciences, said the point is timing. Amyloid and tau, he said, "are observable at relatively late stages of the disease."

About 10% of the elderly may qualify as super agers, depending on the criteria used.

What the researchers say is still unknown

Zhang floated transcranial magnetic stimulation or cognitive training as ways to nudge a brain toward the resilient pattern. His own caveat is blunt. Those interventions have not been tested for cognitive decline, and it is not known whether shifting brain patterns would change where the disease goes.

TMS has shown promise in altering brain activity to treat depression. That is a different condition.

The Stanford work is a risk-sorting tool and a set of potential targets. It is not a therapy.

The drug industry is already aiming at tau

Biogen announced Oct. 29 that it will present new data at the 19th Clinical Trials on Alzheimer's Disease (CTAD) Conference, Nov. 16-19 at the Boston Marriott Copley Place. That includes expanded results from the Phase 2 CELIA study of diranersen (BIIB080), an investigational antisense drug designed to reduce production of all tau forms by targeting MAPT mRNA.

Biogen said the CTAD presentation will build on results first reported in July 2026. The company also plans new analyses on its approved drug lecanemab (Leqembi). The FDA granted diranersen Fast Track designation in 2025. Biogen licensed it from Ionis Pharmaceuticals in December 2019.

The UCSF study did not test diranersen or any other drug, and Biogen's announcement does not tie the drug to these findings. But the overlap is plain. If tau is the more aggressive driver in younger patients, the timing of any tau-lowering therapy could matter most for them. Chiotis said as much about delays.

Whether diranersen slows decline is the open question. Biogen's CELIA data are due in Boston in under two weeks.