First Evidence That Targeting Tau May Slow Cognitive Decline

 Are your competent? doctor and hospital closely following this? NO? So, incompetent in not caring about preventing dementia from your stroke!

First Evidence That Targeting Tau May Slow Cognitive Decline

LONDON — The investigational tau-targeting therapy diranersen (BIIB080) reduced tau pathology and showed evidence of slowing cognitive decline in people with early Alzheimer's disease (AD) in the phase 2 CELIA trial. 

Although the study did not meet its primary endpoint, it demonstrated robust biomarker effects across all doses, with the strongest clinical benefit observed at the lowest dose evaluated.

The new results follow a phase 1b study that showed the drug had a robust impact on tau biomarkers.

“This is the first randomized phase 2 trial of a tau-targeting agent to show that a reduction in tau pathology, which has been clearly and consistently shown across both trials, may slow early Alzheimer's progression,” said study investigator Catherine Mummery, PhD, professor of clinical neurology at the University College London (UCL) Queen Square Institute of Neurology.

Key Points

• Diranersen (BIIB080) ↓ tau pathology in early AD; phase 2 CELIA.
• Primary endpoint missed; no significant dose-response on CDR-SB (P=.21).
• 60-mg dose showed best clinical signal: CDR-SB ↓26%, ADAS-Cog13 ↓42%, MMSE ↓50%.
• CSF total tau ↓50%-65%; tau PET signal also ↓ across all doses.
• Generally well tolerated; AEs mainly lumbar puncture-related, mild-moderate.

What tau reduction threshold predicts cognitive benefit in early AD?

How does intrathecal tau ASO compare with anti-amyloid therapy?

Which biomarkers best monitor response to tau-lowering therapy?

The findings were presented July 14 at the Alzheimer's Association International Conference (AAIC) 2026.

‘Clear Target Engagement’

AD is a progressive neurodegenerative disorder characterized by the accumulation of amyloid plaques and pathological tau, the latter of which is more closely associated with disease progression and clinical symptoms, Mummery said. 

Although anti-amyloid therapies are available, no tau-targeting therapies have been approved for AD.

Diranersen is an investigational intrathecally administered antisense oligonucleotide (ASO) designed to reduce production of tau protein by targeting microtubule-associated protein tau (MAPT) messenger RNA, thereby lowering both intracellular and extracellular tau.

In a phase 1b study in patients with early AD, diranersen was well tolerated, produced robust reductions in tau biomarkers, and showed favorable trends on exploratory cognitive endpoints. 

"There was a dose-dependent reduction in levels of total tau," with levels falling to about 40% of baseline by week 48 in the 60-mg group and remaining at that level, Mummery said. "So there was a clear target engagement."

The double-blind phase 2 CELIA trial enrolled 416 adults aged 50-80 years with mild cognitive impairment due to AD or mild AD dementia and confirmed amyloid pathology. 

Participants were randomly assigned to intrathecal diranersen 60 mg every 24 weeks, 115 mg every 24 weeks, 115 mg every 12 weeks, or placebo for 76 weeks. Although the numbers were small, exploratory analyses showed positive trends on cognitive tests. 

Baseline characteristics were well balanced across treatment groups. The mean participant age was 68 years, which Mummery noted is slightly younger than that of a typical AD population. 

Primary Endpoint Not Met

Approximately 60% of participants had mild cognitive impairment (MCI) due to AD, while 40% had mild AD dementia. Participants underwent quarterly cerebrospinal fluid (CSF) sampling throughout the placebo-controlled phase of the trial. 

At its conclusion, all participants were invited to enroll in a 2-year long-term extension (LTE) study.

Overall, study retention was high. More than 80% of participants completed the placebo-controlled phase, and 94% enrolled in the long-term extension study, suggesting people “weren't put off by having quarterly intrathecal administration of the drug," Mummery said. 

The primary endpoint was dose response for change from baseline to week 76 in the Clinical Dementia Rating — Sum of Boxes (CDR-SB), a global measure of cognition and daily function. 

Although the 60-mg dose slowed decline on the CDR-SB by 26% compared with placebo, the trial did not meet its primary endpoint of demonstrating a dose-response relationship across treatment groups (P = .21).

Analyses of the CDR-SB subdomains also showed consistent improvements in both cognitive and functional domains with the 60-mg dose, Mummery said.

Although the trial missed its primary endpoint, secondary cognitive outcomes consistently favored diranersen. On the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), all three dose groups showed less decline than placebo, with the greatest effect seen in the 60-mg group (42% slower decline; P = .01). A similar pattern was observed on the Mini-Mental State Examination (MMSE), where the 60-mg dose slowed decline by 50% vs placebo (P = .01).

In contrast, the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory for Mild Cognitive Impairment (ADCS-ADL-MCI) showed no significant difference between the 60-mg dose and placebo, suggesting that the functional findings warrant further study, Mummery said. 

‘Unprecedented’ Tau Reduction

Biomarker analyses showed robust target engagement. Cerebrospinal fluid (CSF) total tau levels remained stable in the placebo group but fell by 50% to 65% from baseline across all three diranersen dose groups. Most of the reduction occurred during the first 12 months and was sustained through the remainder of the study, Mummery reported.

Tau PET standardized uptake value ratio (SUVR) analyses showed the expected increase in whole-brain gray matter tau burden in the placebo group over time. In contrast, all three diranersen dose groups showed reductions in tau PET signal, which Mummery described as "unprecedented."

Referring to a brain scan from a participant receiving the 60-mg dose, Mummery highlighted the drug's effect on tau pathology. "In brain areas with particularly high levels of tau, like the lateral temporal and inferior parietal, you see quite a marked reduction," she said.

The drug was generally well tolerated. Most adverse events were mild to moderate in severity and did not result in treatment discontinuation or study withdrawal.

The most common adverse events were procedural pain, post-lumbar puncture syndrome (including headache and low back pain), and confusional state. Mummery noted that post-lumbar puncture syndrome is "incredibly common" in trials involving intrathecal administration. 

In 2025, the FDA granted Fast Track designation to diranersen for the treatment of AD. 

During the discussion, a conference delegate asked about the episodes of confusion reported in the trial. Mummery said investigators "are actively collecting data to try and understand more about it." She emphasized that most cases were mild or moderate, resolved within a week, and rarely led to treatment discontinuation. 

Asked whether a threshold of tau reduction is needed before a clinical benefit emerges, Mummery said important questions remain. "The fact that we're starting to see changes on tau-PET is really exciting, but we're going to learn a huge amount more about what the threshold is and how long it takes for that to mean something," she said.

Encouraging Findings, Important Caveats

The most interesting and noteworthy aspect of the study is that it demonstrates diranersen's ability to effectively reduce tau production, Jessica Langbaum, PhD, senior director of Alzheimer's prevention and research at Banner Alzheimer's Institute, told Medscape Medical News. 

Langbaum said the findings could open the door to therapies for other tauopathies, particularly if future technologies enable tau-targeting drugs to cross the blood-brain barrier and be administered subcutaneously. 

These findings provide the first evidence from a randomized trial that a tau-targeting therapy can produce both robust biomarker effects and a signal of clinical benefit, Laura Nisenbaum, PhD, interim chief science officer at the Alzheimer's Drug Discovery Foundation, said in a press release.

“Tau is one of the two defining pathologies of Alzheimer’s disease and has long been difficult to target, which makes these results all the more notable.”

However, Nisenbaum said the discordance between the biomarker and clinical findings raises important questions about the optimal degree of tau reduction and the dose of diranersen that should be evaluated in future studies. "Those questions will be central to designing the strongest possible phase 3 program."

Mummery has served as a consultant to Alector, Aerska, Biogen, Eisai, Ionis, Lilly, MSD, Neuroimmune, Novartis, Prevail, Roche/Genentech, Switch, Voyager, and Wave. She has received honoraria for teaching and educational activities from Biogen, Eisai, and Lilly, and an academic research funding award from Biogen. She is supported by the NIHR University College London Hospitals Biomedical Research Centre.

Alcohol Alters Brain Flexibility Based on Hidden Dementia Markings

 Ask your competent? doctor for the EXACT LIMITS on your alcohol consumption if you're doing it(like me) to increase your social connections and thus prevent dementia! NO answer or just a blank stare; INCOMPETENCE! Fire them!

Alcohol Alters Brain Flexibility Based on Hidden Dementia Markings

Summary: A new study focused on the corticostriatal circuit, a critical neural pathway governing decision-making, goal-directed behavior, and behavioral flexibility. Using animal models representing isolated features of the disease, the team discovered that alcohol dramatically reduces communication in the presence of amyloid-beta, but significantly amplifies circuit communication in the presence of tau. This unexpected divergence proves that everyday exposures can interact with pre-existing biological conditions in entirely non-linear ways.

Key Facts

• The Cognitive Overlap: Behavioral flexibility is heavily impaired in both substance addiction and early-stage Alzheimer’s disease. This operational overlap prompted the Wang lab to investigate whether alcohol use alters the specific brain circuits targeted during early dementia progression.
• The Additive Assumption Upended: Because amyloid-beta pathology naturally causes abnormal spikes in neural activity and tau causes depressed communication, researchers assumed alcohol would act as a simple additive risk factor, pushing each condition further in its existing path. Instead, alcohol triggered the exact opposite pattern.
• The Amyloid Suppression: In animal models characterized by amyloid-beta accumulation, alcohol exposure severely decreased signaling communication across the corticostriatal pathway.
• The Tau Amplification: In stark contrast, when applied to models defined by tau protein tangles, alcohol exposure sharply increased signaling communication within the exact same brain highway.
• Microglia Immune Disruption: Beyond altering circuit-level communication, the study revealed that alcohol actively interferes with microglia, the resident immune cells of the brain. In the amyloid-dominated models, alcohol disrupted the microglia’s ability to clean up and respond to toxic amyloid buildup.
• Rejecting Uniform Profiles: These findings emphasize that Alzheimer’s disease is not a uniform condition. Because human patients carry completely different ratios of amyloid and tau depending on their genetics, lifestyle, and disease stage, a person’s neurological response to alcohol will vary significantly based on their unique internal pathology.

Source: Texas A&M

Alcohol use has been associated with an increased risk of cognitive decline and dementia. But new research from the Texas A&M University Naresh K. Vashisht College of Medicine at Texas A&M Health suggests the relationship between alcohol and Alzheimer’s disease is more complicated than previously thought.

Instead of affecting all Alzheimer’s-related brain changes in the same way, alcohol interacted differently with amyloid-beta-related and tau-related pathology in animal models, two key pathological processes involved in Alzheimer’s disease.

Alcohol exposure triggers opposite signaling behaviors within the brain’s corticostriatal circuit depending on the presence of amyloid-beta or tau protein hallmarks, shattering the long-standing medical assumption that lifestyle risk factors induce a uniform additive effect on dementia progression. Credit: Neuroscience News

The study was led by postdoctoral research associate Dr. Yufei Huang in the lab of Dr. Jun Wang, professor in the Department of Neuroscience and Experimental Therapeutics. The researchers focused on how alcohol affects brain circuits that are important for behavioral flexibility, or the ability to adjust behavior when situations change. This ability often becomes impaired in both addiction and Alzheimer’s disease.

“We started thinking about whether the same circuits involved in flexibility and adaptation might also be important in Alzheimer’s disease,” Huang said.

The team studied a brain circuit called the corticostriatal circuit, which helps control decision-making and behavioral flexibility. When this circuit does not work properly, people may struggle to adapt to new information or changing environments.

To test the effects of alcohol, the researchers used animal models that represent different Alzheimer’s-related pathological features. One model was based on amyloid-beta, a protein that forms plaques in the brain. The other was based on tau, a protein that forms tangles inside brain cells.

What they found surprised them.

Alcohol affected communication differently in the corticostriatal circuit, a major neural pathway involved with goal-directed behaviors. In animal models with amyloid-beta pathology, alcohol reduced communication in the circuit. In those with tau pathology, alcohol increased communication in the same circuit. In other words, the same exposure led to opposite effects depending on the type of Alzheimer’s-related change present.

“This finding was a complete surprise to us,” Huang said. “We expected alcohol to worsen both conditions in a similar way, but that was not what we saw.”

The researchers explained that amyloid-beta and tau affect the brain differently. Amyloid-beta pathology is often associated with abnormal increases in neural activity, whereas tau pathology is frequently linked to decreased communication between brain cells.

Based on these known differences, the team initially expected alcohol to push each model further in its existing pathological direction—increasing circuit communication in the amyloid-beta model and decreasing it in the tau model. Instead, alcohol produced the opposite pattern, reducing communication in the amyloid-beta model while increasing it in the tau model.

“The results were almost the opposite of what we expected,” Huang said. “To us, this highlights an important principle in biology: Combining two risk factors does not always produce a simple additive effect.”

The study adds to a growing understanding that Alzheimer’s disease is not a single, uniform condition. Different people may have different combinations of disease stage, pathology, genetics and lifestyle factors, which could influence how the brain responds to outside factors such as alcohol.

“This is important because Alzheimer’s disease is not a uniform condition,” Huang said. “People may differ in disease stage, type of brain changes, genetics and lifestyle factors.”

The study also highlights an unexpected link between Alzheimer’s research and addiction science. The Wang lab has long studied how substances like alcohol affect brain circuits involved in learning and decision-making. Those studies showed that substance use can lead to long-term changes in brain flexibility, which is also affected early in Alzheimer’s disease.

That overlap led researchers to ask whether alcohol might also influence Alzheimer’s-related brain changes.

Beyond effects on brain signaling, the study also found that alcohol may interfere with immune cells in the brain, especially in the amyloid model. These immune cells, called microglia, help maintain brain health and respond to disease-related changes such as amyloid accumulation.

“Alcohol not only altered brain circuit function but also appeared to disrupt immune cell responses in the brain,” Huang said. “This may be one way alcohol contributes to Alzheimer’s-related brain dysfunction.”

While the study was done in animal models, the researchers say the findings raise important questions for human health. Alcohol may not affect everyone with Alzheimer’s risk in the same way. People who already have early disease-related brain changes, or who carry genetic risk factors, may respond differently to alcohol exposure.

The team hopes future studies will look at alcohol use in people alongside brain biomarkers such as amyloid, tau and inflammation markers. This could help clarify whether alcohol has different or stronger effects in people who are already in the early stages of Alzheimer’s disease.

For now, the study adds to a growing understanding that brain health is shaped by a combination of biology, environment and lifestyle. Alcohol, rather than having a single effect on the brain, may interact with existing conditions in ways that are more complex than once thought.

Ultimately, the researchers say the goal is not only to understand Alzheimer’s disease better, but also to better understand how everyday exposures may shape brain health over time.

Funding: This research was supported by funding from the National Institute on Alcohol Abuse and Alcoholism (NIAAA/NIH; U01AA025932, R01AA027768, and R01AA030293) and the Texas A&M University Division of Research Targeted Proposal Teams (TPT) funding program.

Key Questions Answered:

Q: Why did scientists expect alcohol to affect amyloid-beta and tau proteins in the exact same way?

A: Traditionally, air pollution, high blood pressure, and alcohol use have been treated as generic risk factors that simply worsen brain health across the board. Because both amyloid plaques and tau tangles are toxic to brain tissue, researchers naturally assumed that adding alcohol to the mix would act like pouring gasoline on a fire, speeding up the damage uniformly. Discovering that alcohol actually dials down brain communication in one model while winding it up in the other was a complete biological surprise.

Q: What is behavioral flexibility, and why is this specific brain circuit so important?

A: Behavioral flexibility is your brain’s ability to smoothly change its strategy or choices when your environment shifts. The corticostriatal circuit is the primary brain highway that controls this decision-making process. When this circuit is damaged or altered, individuals get “stuck” in repetitive loops and struggle to process new information. Because this flexibility breaks down very early in both alcohol addiction and Alzheimer’s disease, understanding how they intersect is crucial to protecting adult cognitive health.

Q: Does this mean alcohol could actually be good for certain types of Alzheimer’s patients?

A: Absolutely not. While alcohol caused an unexpected surge in communication within the tau model, an abnormal spike in signaling can be just as toxic and damaging to brain networks as a drop in communication. Dr. Yufei Huang stresses that the real takeaway is that combining two different health risks doesn’t produce a simple, predictable outcome. Instead of showing that alcohol is beneficial, the study proves that everyday lifestyle exposures interact with our unique internal biology in highly complex, unpredictable ways.

Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this Alzheimer’s disease research news

Author: Laura Tolentino
Source: Texas A&M Health
Contact: Laura Tolentino – Texas A&M Health
Image: The image is credited to Neuroscience News

Original Research: Open access.

“Chronic alcohol exposure produces pathology-dependent corticostriatal circuit remodeling in Aβ- and tau-based mouse models of Alzheimer’s disease” by Himanshu Gangal, Jianrong Li, Jun Wang, Ruifeng Chen, Xuehua Wang, Xueyi Xie, Yufei Huang, Zhenbo Huang. Neuropharmacology
DOI:10.1016/j.neuropharm.2026.111069

Midlife Vitamin D Levels Linked to Later Tau-PET Deposition

 I just exited midlife at age 70, so my stuff is already baked in. But then I have way more than 16 years to go, so maybe still time.

Midlife Vitamin D Levels Linked to Later Tau-PET Deposition

 Higher circulating vitamin D levels in early midlife are associated with lower tau deposition on brain positron emission tomography (PET) imaging in later midlife among adults without dementia, according to a study published in Neurology Open Access. In a prospective cohort study of adults without dementia from the Framingham Heart Study Generation 3 cohort, researchers evaluated whether serum 25-hydroxyvitamin D measured in early midlife is associated with later tau and amyloid burden on brain PET imaging.Serum 25-hydroxyvitamin D levels were assessed at examination cycle 1 between 2002 and 2005. Participants subsequently underwent amyloid PET and/or tau PET imaging between 2016 and 2019. [H]igher vitamin D levels in midlife may offer protection against pathologic tau deposition in the brain, while low vitamin D may represent a potentially modifiable risk factor for healthy middle-aged individuals seeking to reduce dementia risk. A total of 793 participants were included, of whom 53% were women, and the mean [SD] age was 39 [8] years. Of the participants, 424 underwent amyloid PET imaging, and 369 underwent tau PET. The mean (SD) interval between vitamin D measurement and PET imaging was 16.2 (2.4) years. Outcomes included global and composite tau-PET burden and amyloid-PET burden. In fully adjusted models, higher serum 25-hydroxyvitamin D levels were associated with lower global tau-PET burden (β=−0.022; 95% CI, −0.040 to −0.004;P=.010) and lower composite tau-PET burden (β=−0.023; 95% CI, −0.043 to −0.003;P=.016). In contrast, serum 25-hydroxyvitamin D levels were not associated with amyloid-PET burden (β=0.001; 95% CI, −0.024 to 0.024;P=.987). When analyzed using a clinical cutoff (<30 vs ≥30 ng/mL), serum 25-hydroxyvitamin D levels were not significantly associated with tau or amyloid PET outcomes in fully adjusted models. Baseline mean (SD) serum 25-hydroxyvitamin D level was 38 (15) ng/mL, with 34% of participants below 30 ng/mL. Sensitivity analyses excluding individuals taking vitamin D supplements yielded similar findings, with persistent associations between higher serum 25-hydroxyvitamin D and lower tau burden. Study limitations include a lack of repeated vitamin D measurements over time, and the long interval between vitamin D assessment and PET imaging, which may introduce exposure misclassification. This study suggests that higher vitamin D levels in midlife may offer protection against pathologic tau deposition in the brain, while low vitamin D may represent a potentially modifiable risk factor for healthy middle-aged individuals seeking to reduce dementia risk,” concluded the authors.

Higher Education May Be a Double-Edged Sword in Alzheimer's

 So, is my almost Master's the best of both worlds?

Higher Education May Be a Double-Edged Sword in Alzheimer's

Key Takeaways

• Higher education was tied to slower tau accumulation at amyloid-negative stages but accelerated accumulation at amyloid-positive stages.
• Differences in tau accumulation between education levels varied across multiple brain regions.
• The findings do not contradict other data linking higher education with greater cognitive reserve, the researchers pointed out.

Higher education appeared to protect against tau accumulation during the amyloid-negative stages of Alzheimer's disease but was associated with accelerated tau accumulation in amyloid-positive stages, data from three cohorts suggested.

In amyloid PET-negative groups, people who achieved higher education had slower tau accumulation than those with lower education (right middle temporal gyrus, P=0.03).

In amyloid PET-positive groups, however, more education was tied to faster tau accumulation (left middle temporal gyrus, P=0.03), said Tengfei Guo, PhD, of the Shenzhen Bay Laboratory in China, and colleagues. This group also had greater connectivity-associated tau spread compared with people with less education (P=0.048).

Differences in tau accumulation in people with high versus low education varied significantly between amyloid-positive and amyloid-negative groups in the left anterior middle temporal gyrus (P=0.007), inferior temporal gyrus (P=0.03), right parieto-occipital sulcus (P=0.04), and superior peripheral visual area (P=0.04), the researchers reported in JAMA Neurologyopens in a new tab or window.

Amyloid-targeted treatment with solanezumab appeared to mitigate plasma phosphorylated-tau217 (p-tau217)-associated tau accumulation in people with higher education who had Alzheimer's, they noted.

"This multimodal, multicenter, and multiethnic cohort study highlighted the dual role of higher educational attainment in tau accumulation," Guo and co-authors wrote.

"The findings also underscore the potential of amyloid beta-targeting treatment at preclinical stages to slow tau progression in patients with Alzheimer's disease, particularly those with higher educational attainment," they added.

Education -- a proxy for cognitive reserve -- often correlates with better cognition, greater gray matter volume, improved network efficiency, and enhanced inter-network brain connectivity in older adults, Guo and colleagues observed.

"However, its association with Alzheimer's disease pathologies, particularly tau, remains underexplored," they said. "Although some studies found no significant association, others suggest that higher educational attainment may correlate with greater tau burden in temporoparietal regions in Alzheimer's disease.

The analysis included data from 887 people across three independent cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNIopens in a new tab or window, 377 participants; mean age 73), the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4opens in a new tab or window) study of solanezumab in amyloid-positive people and its companion LEARN study of amyloid-negative people (395 participants; mean age 72), and the Greater Bay Area Healthy Aging Brain Study (GHABSopens in a new tab or window, 115 participants; mean age 66).

ADNI and GHABS represented Northern American and Southern Chinese populations, respectively; A4 was a multicenter trial. Participants had amyloid and tau PET imaging; a subset also had plasma p-tau217 measures.

Participants were dichotomized into high or low education status based on their cohort-specific median years of education in either the amyloid-negative group (17, 16, and 14 years, respectively, for ADNI, LEARN, and GHABS) or the amyloid-positive group (16, 16, and 11 years for ADNI, A4, and GHABS).

The findings do not contradict epidemiological evidence that links higher education with greater cognitive reserve and less risk of developing dementia, Guo and co-authors pointed out.

"A recent studyopens in a new tab or window by our group showed that higher educational attainment was associated with greater brain reserve, potentially delaying the onset of significant brain atrophy by a median of 1.9 years," they wrote. "We hypothesize that the cognitive benefits of higher educational attainment stem from greater brain reserve developed early in life, which helps buffer against cognitive decline."

Other theoriesopens in a new tab or window "similarly propose that higher educational attainment fosters brain reserve, providing individuals with more to lose as the disease progresses," Guo and co-authors noted.

"Notably, our significant findings were predominantly observed in individuals with cognitive impairment," they added.

The study had several limitations, the researchers acknowledged. Regional results from 200 brain regions of interest did not survive multiple comparison corrections. "Despite this, the highly consistent findings across cohorts suggest a modest association between higher educational attainment and tau accumulation, warranting cautious interpretation," they wrote.

The GHABS study lacked longitudinal tau-PET scans, limiting validation of the ADNI and A4 findings, they added.

Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures

This study was funded by grants from the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Science Foundation for Distinguished Young Scholars, and the Shenzhen Bay Laboratory.

Guo reported receiving travel funds to attend the 2023 Alzheimer's Association International Conference and serving on the editors' board of Alzheimer's & Dementia journal. Co-authors had no disclosures.

Primary Source

JAMA Neurology

Source Reference: opens in a new tab or windowCai Y, et al "Higher educational attainment and accelerated tau accumulation in Alzheimer disease" JAMA Neurol 2025; DOI: 10.1001/jamaneurol.2025.1801.