The New Alzheimer Biomarker versus Nuns Who Defied Dementia

Brain scientists have been looking for biomarkers to predict who will develop dementia. For decades researchers relied upon autopsy analysis to identify amyloid plaque in the brain to diagnose Alzheimer disease post mortem. More recently, investigators have used PET scans to detect amyloid in the brain, but such imaging is expensive. Now, an Alzheimer biomarker called phosphorylated tau 217, or p-tau217, is generating enormous excitement in the neuroscience community. A new study in JAMA (July 14, 2026) suggests that elevated levels may help identify cognitively healthy older people who face an increased risk of memory and thinking problems during the years ahead.

A little over a year ago the FDA cleared a “Blood Test Used in Diagnosing Alzheimer’s Disease.”

“New Test Provides Less Invasive Option, Reduces Reliance on PET Scans and Increases Diagnosis Accessibility”

That sounds like a breakthrough—and it may be.

The Nun Study and Why It Challenges Conventional Thinking

Before anyone concludes that a blood test can foretell an individual’s cognitive future, we need to revisit one of the most remarkable investigations in the history of Alzheimer disease: the Nun Study. We were fortunate enough to interview Dr. David Snowdon on June 23, 2001, on our People’s Pharmacy radio show. He initiated the Nun Study in 1986.

The volunteers belonged to the School Sisters of Notre Dame. Eventually 678 joined the study. Dr. Snowdon wanted to learn how a number of variables affected brain health as the women aged.

Some of the nuns in that study died with brains containing extensive plaques and tangles, the classic pathological hallmarks of Alzheimer disease. Nevertheless, they had remained cognitively intact during life. When they died, their brains were carefully examined for signs of pathology.

Dr. Snowdon explained to us that their brains appeared badly damaged under a microscope. But their minds had continued working surprisingly well. How can we reconcile those seemingly contradictory observations?

What Is the P-Tau217 Alzheimer Blood Biomarker?

Tau is a protein that normally helps support the internal structure of nerve cells. In Alzheimer disease, tau undergoes chemical changes, including phosphorylation, and can accumulate inside neurons as neurofibrillary tangles.

p-tau217 is tau that has been phosphorylated at a particular location—the amino acid threonine 217. Elevated concentrations in blood are strongly associated with amyloid accumulation in the brain and, to some extent, with tau pathology.

We have written extensively about amyloid plaque and Alzheimer disease. That’s because the pharmaceutical industry has been extremely successful at developing anti-amyloid drugs. As effective as these drugs are at ridding the brain of amyloid plaque, they do not reverse the signs and symptoms of Alzheimer disease. People continue to decline. Should you wish to learn more about this contradiction, here is a link:

Anti-Amyloid Drugs: Breakthrough or Boondoggle Against Alzheimer’s?

In May 2025, the FDA cleared the first blood test to aid in diagnosing Alzheimer disease. The Lumipulse test measures both p-tau217 and beta-amyloid 1-42 and calculates a ratio between them. There is an important catch. The FDA clearance applies to people age 55 or older who are already showing signs or symptoms of cognitive decline.

The test is supposed to be interpreted along with the person’s medical history, cognitive evaluation and other clinical information. The FDA specifically states that the test is not intended as a screening test or as a stand-alone diagnosis.

Here is the FDA announcement:

“FDA Clears First Blood Test Used in Diagnosing Alzheimer’s Disease“

That is different from using p-tau217 to tell an apparently healthy person what will happen five or 10 years from now.

Can an Alzheimer Blood Biomarker Predict Cognitive Decline?

Researchers writing in JAMA on July 14, 2026, attempted to answer that question.

They pooled information from 2,684 cognitively unimpaired older adults enrolled in six observational studies and clinical trials in North America, Japan and Australia. The median age was approximately 70, and the participants were followed for a median of 5.4 years. Some were followed for as long as 13.5 years.

During that time, 478 participants progressed to some form of cognitive impairment. The outcome included mild cognitive impairment, dementia or repeated ratings indicating that cognitive function was no longer completely normal.

Higher p-tau217 levels were associated with greater risk. For every one-standard-deviation increase in p-tau217, the relative risk of progressing to cognitive impairment rose by 38 percent.

The researchers also translated the findings into something people can understand more readily: absolute risk. Readers of The People’s Pharmacy have learned that absolute risk is a key metric.

“We also estimated absolute risk across the different p-tau217 categories for the 3 time horizons (2, 5, and 10 years). Two-year absolute risk was found to be very low regardless of the p-tau217 category.”

Over five years:

• People in the low p-tau217 group had about a 12 percent risk of developing cognitive impairment.
• Those with intermediate p-tau217 levels had about a 15 percent risk.
• Those with high p-tau217 had approximately a 24 percent risk.
• Those with very high p-tau217 had an estimated 38 percent risk.

These are impressive findings. They suggest that p-tau217 is not merely a snapshot of abnormal proteins. At the group level, it provides information about the likelihood of subsequent cognitive decline.

But “increased risk” is not the same as destiny.

Even among people with very high p-tau217, approximately 62 percent did not progress to cognitive impairment during the five-year period. Conversely, even the low p-tau217 group had a 12 percent risk of cognitive decline.

That tells us that p-tau217 is detecting something important. It is not telling the whole story.

The Alzheimer Blood Biomarker Measures Risk, Not Fate

A biomarker is a measurable biological sign. Blood pressure is a biomarker. So are LDL cholesterol, blood sugar, prostate-specific antigen (PSA) and liver enzymes.

Biomarkers can be extremely useful. They can help doctors detect disease, estimate risk, select treatments or monitor whether a therapy is producing a biological effect.

But biomarkers do not necessarily identify the original cause of a disease. Nor do they always predict how a particular person will feel or function.

High LDL cholesterol increases the probability of cardiovascular disease, but it cannot tell us precisely who will suffer a heart attack or when it will occur. An abnormal prostate-specific antigen (PSA) level does not by itself prove that a man has prostate cancer. And a “normal” PSA result does not always mean a man is free of prostate cancer.

Likewise, p-tau217 can reflect the biological processes associated with Alzheimer disease without serving as a crystal ball for an individual’s cognitive future.

Scientists are still debating where phosphorylated tau belongs in the chain of events that leads to Alzheimer disease. Amyloid accumulation may trigger changes in tau, inflammation, immune activity, blood vessels, metabolism and neuronal function. Tau pathology may then contribute directly to the loss of synapses and nerve cells.

It is also possible that amyloid and abnormal tau are part of a much larger biological cascade rather than the sole explanation for dementia.

The new JAMA study was observational. It demonstrates an association between p-tau217 and later cognitive impairment. It does not establish that circulating p-tau217 caused the cognitive decline.

The Nun Study Complicates the Alzheimer Story

The sisters who participated in the Nun Study agreed to undergo annual memory and cognitive testing. Researchers were given access to their medical records, educational histories, academic transcripts and autobiographies written when many of the women were young. As mentioned, the participants agreed to donate their brains after death.

The communal lives of the sisters gave researchers an unusual opportunity. The participants had relatively similar housing, nutrition, medical care, smoking histories, alcohol exposure and social support. That reduced some of the differences that make long-term aging studies so difficult to interpret.

The study eventually achieved an extraordinary brain-donation rate of approximately 98 percent.

A comprehensive 30-year review of the Nun Study was published in Alzheimer’s & Dementia (Feb. 25, 2025).

The Nun Study confirmed that amyloid plaques and neurofibrillary tangles are strongly associated with cognitive decline. In particular, the distribution of tau tangles—measured by what pathologists call Braak staging—was closely related to dementia.

That part fits the conventional Alzheimer narrative. But not every brain followed the script.

When Alzheimer Pathology Does Not Produce Dementia

Some sisters had substantial Alzheimer-type pathology at autopsy but had remained cognitively intact during life. Researchers have used terms such as “asymptomatic Alzheimer disease,” “cognitive resilience” and “cognitive reserve” to describe this phenomenon.

The finding does not mean that plaques and tangles are harmless. Across populations, heavier pathological burdens are associated with a greater likelihood of dementia. It does mean that the relationship is not one-to-one.

One person may develop serious cognitive problems with a relatively modest amount of pathology. Another may tolerate much more extensive damage without meeting the clinical criteria for dementia.

Researchers examining brains from cognitively resilient nuns found several possible explanations. Resilient individuals tended to be younger at death, had fewer additional brain diseases and had less extensive tau involvement in the neocortex.

One particularly intriguing investigation found enlargement of nerve-cell bodies, nuclei and nucleoli in the hippocampus of women who had Alzheimer pathology without cognitive impairment. The researchers proposed that this neuronal enlargement might represent a compensatory response—an attempt by surviving neurons to work harder in the presence of disease.

That remains a hypothesis, but it raises a profound possibility: the brain may have ways to compensate for pathology that our current blood tests do not measure.

A Brain Can Harbor More Than One Disease

The Nun Study also demonstrated that dementia in old age is rarely as tidy as a textbook diagram. Many brains contained several pathologies at the same time. In addition to plaques and tangles, researchers found strokes, small-vessel damage, hippocampal sclerosis, Lewy bodies and abnormal TDP-43 protein.

These additional problems mattered. Small strokes dramatically increased the likelihood that a sister with Alzheimer pathology would develop dementia. Alzheimer lesions and cerebral infarcts appeared to arise independently, but together they were far more damaging than either process alone.

The study also helped characterize hippocampal sclerosis of aging and what is now called limbic-predominant age-related TDP-43 encephalopathy, or LATE. Both can impair memory and may masquerade as, accompany or intensify Alzheimer disease.

This helps explain why an Alzheimer blood biomarker cannot provide a complete forecast. A person’s cognitive future may depend not only on amyloid and tau, but also on blood-vessel health, inflammation, other abnormal proteins, neuronal reserve and the brain’s capacity to compensate. In addition, we have written a lot about brain infections. Here is just one such article:

Amyloid or Infection Is Contributing to Alzheimer’s
We have been losing the war against Alzheimer’s disease for decades. If infection is contributing to Alzheimer’s, we can do better!

The JAMA editorialists make a similar point. They caution that future prediction models will need to account for kidney disease, vascular and metabolic conditions, other neurodegenerative pathologies and the competing risk of death.

Cognitive Reserve: How Can the Brain Keep Working?

One of the most famous Nun Study findings came not from brain tissue, but from autobiographies the sisters had written as young women. Researchers analyzed the writing for “idea density”—roughly, how much information was packed into each sentence. Sisters whose early writing contained greater idea density generally performed better on cognitive tests many decades later and were less likely to develop dementia.

Education also appeared to provide some protection. Most of the sisters were highly educated, and many had worked as teachers.

This research contributed to the concept of cognitive reserve. The idea is that education, mental activity, language ability and a lifetime of intellectual engagement may allow the brain to operate more efficiently or develop alternative networks.

Cognitive reserve may not prevent plaques or tangles from forming. Instead, it may help a person continue functioning despite them. The distinction is crucial. A biomarker may tell us something about the amount of biological pathology. It may tell us far less about the brain’s ability to withstand or work around that pathology.

What the New Alzheimer Biomarker P-Tau217 Study Does—and Does Not—Show

The new JAMA research deserves to be taken seriously. It included thousands of carefully studied people from several cohorts and produced understandable estimates of absolute risk over defined periods.

It shows that high p-tau217 is a warning sign.

It does not show that:

• Everyone with a high result will develop dementia.
• A normal result guarantees lifelong cognitive health.
• P-tau217 is the original cause of Alzheimer disease.
• A blood test can measure cognitive reserve.
• Testing cognitively healthy people currently improves their medical care.
• Treatment based on an elevated result will prevent dementia.

The study participants were also not a random sampling of the public. Many were highly educated research volunteers. The researchers standardized results from several different p-tau217 assays, so the categories used in the study cannot automatically be translated into a single commercial laboratory cutoff.

Kidney disease can also affect p-tau217 concentrations. Other illnesses and age-related brain pathologies may alter the relationship between a blood result and an individual’s true risk.

For all these reasons, both the investigators and the editorialists stress that the findings are not yet ready to provide precise personal predictions for cognitively normal people.

Should Healthy People Request an Alzheimer Blood Biomarker?

At the moment, major clinical recommendations do not endorse Alzheimer biomarker testing for cognitively unimpaired people outside research studies or clinical trials.

There is no FDA-approved disease-modifying treatment for people who have abnormal biomarkers but no cognitive symptoms. A positive result could therefore produce years of fear without offering a clear course of action. It might also lead to additional PET scans, spinal taps or inappropriate treatment.

For someone who is experiencing objective memory or thinking problems, blood-based biomarkers may become extremely valuable as part of a comprehensive evaluation. They could reduce the need for more expensive or invasive testing and help distinguish Alzheimer disease from other causes of cognitive decline.

But ordering such a test merely because someone is getting older is a different proposition. Before testing, a person should understand exactly what the assay measures, why it is being ordered, what a positive or negative result would mean and whether the result would change any medical decision.

The People’s Pharmacy Perspective

The enthusiasm surrounding p-tau217 is understandable. For more than a century, doctors often had to wait until autopsy to see the plaques and tangles associated with Alzheimer disease. A relatively simple blood test that might detect the biological footprint of those changes is an important scientific advance.

But a footprint is not the traveler. The Nun Study reminds us that the human brain is more resilient, more complicated and perhaps more mysterious than any single laboratory measurement can capture. An Alzheimer blood biomarker can help estimate risk. It cannot yet tell an individual exactly how well the mind will work five or 10 years from now.

Amyloid and phosphorylated tau matter. So do strokes, small-vessel disease, TDP-43, hippocampal sclerosis, education, early language ability and the brain’s ability to compensate for damage. Should you wish to learn more about other contributors to dementia and ways to prevent decline, why not listen to our interview with Dale Bredesen, MD. He is the Senior Director of Precision Brain Health at Pacific Neuroscience Institute, and former Professor of Molecular and Medical Pharmacology at UCLA. Dr. Bredesen is also the founding President and CEO of the Buck Institute for Research on Aging and the Co-founder of MPI Cognition. Dr. Bredesen is the author of the New York Times best seller The End of Alzheimer’s: The First Program to Prevent and Reverse Cognitive Decline and The First Survivors of Alzheimer’s: How Patients Recovered Life and Hope in Their Own Words.

Here is a link to the interview:

Show 1412: Beyond Amyloid: The Science That Could Change the Course of Alzheimer Disease
A personalized approach considering multiple factors may be helpful for changing the course of Alzheimer disease.

One more thing. If you read this article, you will be amazed:

Hidden Memories in Alzheimer’s Disease: Another Amazing Story!
Can hidden memories in Alzheimer’s disease suddenly reappear? New research and reader stories astonish. Will neuroscientists pay attention?

Many healthcare professionals believe that when someone is no longer able to care for themselves, remember people or communicate, the brain has turned to mush. The stories we share above suggest that is not the case. There are also amazing stories about “Terminal Lucidity.” That is when a person nears death and is able to interact with loved ones, communicate clearly and recapture old memories despite years of seeming absence.

We may know far less about the brain than neuroscientists would like to admit. Perhaps the most important lesson from the Nun Study is that brain pathology is not always destiny.

We hope that you found this article of value. Before you move on, we would be ever so grateful if you would share it with friends and family.

We do our best to report the latest medical research, but we also try to go further and provide context. When we interviewed Dr. David Snowdon on June 23, 2001, about the Nun Study, we were impressed with his insights and kindness. Now, 25 years later, reading the summary of the Nun Study in Alzheimer’s & Dementia (Feb. 25, 2025), we are so grateful that we had the opportunity to talk with Dr. Snowdon so long ago.

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