The tau-targeting trials: a promising direction, not yet a treatment
- Richard Moore
- Jul 29
- 14 min read
This blog follows directly from our previous piece, After Amyloid: Why Tau Tracks Alzheimer's Symptoms More Closely, which explains what tau is and why the scientific community has shifted its focus toward it. If you have not read that one yet, it provides the foundation for everything discussed here.
Something has changed in Alzheimer's research, and most people have not heard about It
Behind every clinical trial statistic is someone waiting. A spouse watching their partner lose words. A daughter driving her father to appointments he no longer remembers. A person in their fifties who has just watched a parent receive a diagnosis and is quietly wondering what it means for them.
For those people, the history of Alzheimer's drug development has been one of almost unbroken disappointment. Between 2002 and 2012 alone, approximately 99.6% of Alzheimer's drug programmes failed to reach approval (Cummings et al., 2014).
Then came lecanemab and donanemab, the first drugs to genuinely slow Alzheimer's progression after a 17-year drought (Sabbagh et al., 2024). They were a real step forward. But a quieter revolution has been building alongside them: the race to target tau directly. As of mid-2026, the pipeline of tau-targeting therapies in human trials is broader than it has been at any point in recent Alzheimer's history. Some early results are, carefully and honestly described, genuinely encouraging.
This blog gives you the full picture: what has been tested, what has failed, what is now showing promise, and what none of it yet means for anyone living with Alzheimer's today.
Why Tau? A brief reminder before we get into the science
Tau is a protein that lives inside brain cells. In a healthy brain it keeps the internal transport system running smoothly (think of it as the cell's railway network). In Alzheimer's disease, tau becomes chemically altered and collapses into twisted knots called neurofibrillary tangles, disrupting normal cellular function and contributing to neuronal dysfunction and death (Barbier et al., 2019).
Unlike amyloid plaques, which begin accumulating decades before any symptoms appear, tau tangles correlate more closely with symptom severity and regional cognitive impairment than amyloid burden does (Macedo et al., 2023). Tau is not just a passive indicator of the disease. Where it appears in the brain, and how far it has spread, tends to mirror what a person is actually experiencing. If you could stop tau spreading, in theory you could slow the symptoms that follow. That is the logic driving every trial discussed in this blog (Cowan et al., 2025).
The first wave of tau drugs: what went wrong, and what was learned
Four antibodies: semorinemab (Roche/Genentech), gosuranemab (Biogen), tilavonemab (AbbVie), and zagotenemab (Eli Lilly), were all tested and discontinued. All four targeted the amino-terminal end of tau, essentially the protein's starting section, and all four failed to demonstrate meaningful clinical benefit (Cai et al., 2025; Teng et al., 2022).
A brief analogy helps. Imagine the tau protein as a long key. These first antibodies were all clutching the bow: the flat section you hold, while the region most associated with the damaging clumping process lies further along, in the middle. That central section is called the microtubule-binding region (MTBR). First-generation antibodies had limited engagement with it (Cowan et al., 2025). Even when they successfully cleared tau from the cerebrospinal fluid (CSF), the fluid surrounding the brain and spinal cord, they may have had limited ability to affect established intracellular tangles, and the trial participants continued to decline (Alzforum, 2021).
The field drew two hard lessons from this. The first was to target a different part of tau, specifically the MTBR. The second was to be far more selective about which patients entered trials in the first place, using tau positron emission tomography (tau-PET) imaging and blood biomarkers to confirm early-stage disease rather than relying solely on clinical symptoms, which may emerge only after substantial pathology has already accumulated (Cowan et al., 2025).
The second wave: more precise and more varied strategies
The newer programmes each take a different angle on the same problem. Most try to block or clear tau at the point where it causes damage. One takes a completely different approach by trying to reduce how much tau the brain produces in the first place. What they all share is a far greater emphasis on finding people early, before the disease has taken too firm a hold, using blood tests and brain scans to confirm who is the right candidate rather than waiting for symptoms to make the decision.
Bepranemab: the first encouraging signal, and a story that is not over
Bepranemab, developed by UCB (a global biopharmaceutical company), is the furthest along of the new generation. Its Phase 2a results were presented at the Clinical Trials on Alzheimer's Disease (CTAD) conference in Madrid in October 2024.
The TOGETHER trial (NCT04867616) was a double-blind, placebo-controlled study in 466 people with prodromal to mild Alzheimer's disease. They received bepranemab at two doses, 45 mg/kg and 90 mg/kg, or placebo, for 80 weeks (UCB, 2024).
The honest summary: bepranemab did not meet its primary endpoint. The primary measure, change in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), showed no statistically significant difference between bepranemab and placebo in the full trial population (NeurologyLive, 2024). Bepranemab is not an approved treatment, and this trial did not establish clinical efficacy.
For anyone living with Alzheimer's or caring for someone who is, that sentence deserves to be read slowly. It is the most important sentence in this section, and it comes before the encouraging news, because that is the right order to present it.
But exploratory secondary analyses have given researchers genuine reason to keep going. Put simply: even though the overall clinical test did not show a significant difference, these additional analyses suggested the drug may have slowed the build-up of tau in the brain and shown early signals on a separate cognitive measure. These are exploratory findings from a company announcement rather than a completed, independently replicated trial, and should be interpreted cautiously. Bepranemab reduced the rate of tau accumulation in major brain regions by 33 to 58% compared to placebo on brain imaging, and an exploratory cognitive measure called the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog14) showed a 21 to 25% difference between bepranemab and placebo (UCB, 2024). In a prespecified subgroup of participants who did not carry a gene variant called apolipoprotein E epsilon 4 (APOE-E4), a variant that increases Alzheimer's risk, results were stronger still, though subgroup findings of this kind require replication before firm conclusions can be drawn (UCB, 2024).
This appears to be one of the first tau-antibody trials to report both biological effects and an exploratory cognitive signal in a randomised controlled trial (RCT). The trial has moved into an open-label extension phase; the next question is whether those signals translate into clear clinical benefit over a longer period, in a more precisely selected population (NeurologyLive, 2025).
Etalanetug: targeting how tau spreads between brain cells
Etalanetug (E2814), developed by Eisai in collaboration with University College London, is designed not simply to clear tau but to stop tau seeds, tiny fragments of pathological tau, from seeding pathology in neighbouring brain cells (Andreozzi et al., 2026). Think of it as intercepting the problem before it can take hold in the next cell down the line.
A Phase Ib/II trial in eight people with dominantly inherited Alzheimer's disease (DIAD), a rare, genetically determined form of the disease, showed large reductions in tau biomarkers in the blood and spinal fluid, published in Alzheimer's Research & Therapy in 2026 (Andreozzi et al., 2026). In plain terms: the drug appeared to substantially reduce the measurable signs of tau pathology in the body, with reductions growing larger the longer people were on treatment. Brain scans in three of the participants showed that tau was stable or decreasing rather than continuing to accumulate (Andreozzi et al., 2026).
Eight people is not enough to draw conclusions about clinical effectiveness. Etalanetug has received Fast Track designation from the US Food and Drug Administration (FDA) (Patient Care Online, 2026) and is now being tested in the larger Phase II/III Tau NexGen study and a Phase II study giving etalanetug alongside lecanemab, the first trial to test a combined amyloid-plus-tau approach (Andreozzi et al., 2026).
BIIB080: stopping tau at the source
Here is an idea that stops you when you first encounter it. What if, instead of trying to clear tau after it has already caused damage, you could simply stop the brain from making so much of it in the first place? Every drug discussed so far targets tau protein after it has been made. BIIB080, developed by Biogen, tries to stop tau being produced in the first place: a volume dial rather than a cleanup crew.
BIIB080 is an antisense oligonucleotide (ASO) therapy that targets the messenger ribonucleic acid (mRNA) instruction telling cells to make tau protein. Less instruction, less tau manufactured, less available to misfold and aggregate (Biogen, 2025). It is worth noting that tau is a normal protein that the brain needs in healthy amounts, so whether long-term suppression of tau production is safe remains an important open question that later trials will need to address. In a Phase 1b trial of 46 people with mild Alzheimer's dementia, primarily designed to assess safety and biomarker changes and published in JAMA Neurology, BIIB080 produced dose-dependent reductions of up to 56% in soluble tau in CSF and reduced tau accumulation on PET (Edwards et al., 2023). Exploratory clinical analyses published in Nature Aging in 2026 showed a consistent trend toward slowed decline on cognitive and functional measures in higher-dose groups, though these were not the primary outcomes of the study and the treatment groups were small (Shulman et al., 2026). The FDA granted Fast Track designation in April 2025 (Biogen, 2025). The Phase 2 CELIA trial (NCT05399888) is now fully enrolled, with results expected in 2026 (Pharmacy Times, 2026).
BMS-986446 and MK-2214: the pipeline deepens
BMS-986446, developed by Bristol Myers Squibb, adds a further mechanism: beyond targeting the MTBR, it activates the brain's own immune cells, called microglia, to physically digest tau aggregates through a process called phagocytosis (van Dyck et al., 2025). The FDA granted Fast Track designation in May 2026 (NeurologyLive, 2026a). The TargetTau-1 trial (NCT06268886) enrolled 475 patients across 14 countries, with results expected in 2027.
MK-2214, developed by Merck, entered Phase 2 in July 2025 with 340 participants. Its engineered extended half-life means it remains active in the body longer than a standard antibody, potentially allowing for less frequent dosing, a practical advantage for older patients. Phase 1 data confirmed measurable reductions in phosphorylated tau in CSF (Alzforum, 2025).
The current pipeline includes an unusually broad range of tau-targeting approaches in simultaneous clinical development, using three different biological mechanisms (Cowan et al., 2025).
What the science cannot yet tell us, and what that means for you
If you have read this far, you deserve a straight answer. So here it is: as of mid-2026, no tau-targeting therapy has demonstrated a statistically significant benefit on a primary clinical endpoint in a large randomised controlled trial. Bepranemab's secondary results are encouraging. Etalanetug's biomarker data are striking. BIIB080's clinical trends are promising. But none of these is the same as a treatment that has shown clear benefit for the people who took part. We are not there yet. It is also worth knowing that many of the figures cited in this blog come from company press releases and conference presentations rather than completed, independently replicated Phase III studies. That does not make them wrong, but it does mean they should be treated as preliminary until confirmed in larger, peer-reviewed trials.
Several biological questions also remain unresolved. The bepranemab data suggest that earlier intervention may prove important: that the brain with less established tau pathology responds better, though this still needs to be demonstrated prospectively (UCB, 2024). The etalanetug Study 202 trial is testing whether giving a tau drug alongside an amyloid drug is more effective than either alone (Andreozzi et al., 2026).
A third challenge, rarely discussed openly, is patient selection. Phosphorylated tau 217 (p-tau217) is a form of tau that leaks into the bloodstream as Alzheimer's pathology develops, rising years before symptoms appear. A 2024 systematic review found that p-tau217 assays detected Alzheimer's pathology with sensitivity and specificity of 82 to 86%, varying by assay and population (Khalafi et al., 2024). In a significant development, the FDA cleared the first blood test measuring p-tau217 and amyloid in 2025 for people aged 55 or over who are already showing cognitive symptoms, to be used as part of a specialist clinical assessment (US Food and Drug Administration, 2025). It is important to note that this test is not recommended as a stand-alone screening tool for people without symptoms; results always require specialist interpretation. Think of it as the brain's equivalent of a smoke detector: a powerful signal when used in the right clinical context. The posdinemab trial from Johnson and Johnson found that 79.6% of screened participants failed to meet trial eligibility criteria, most commonly because they lacked elevated p-tau217 in their blood (NeurologyLive, 2026b). Getting the right people into the right trials at the right stage is itself a formidable challenge.
What this means if you or someone you love has Alzheimer's today
The honest answer to "when will there be a tau treatment?" is: we do not know. The science is advancing rapidly, with more approaches in parallel trials than the field has seen before. But clinical trials take years to complete, and positive biomarker results do not automatically translate into treatments that help people in clinic.
What the science does tell us is that several modifiable factors have been associated with dementia risk and overall brain health. Regular physical activity, good sleep, a nutritionally adequate diet, and management of cardiovascular and metabolic risk factors are consistently supported by population-level evidence (Livingston et al., 2024). Some of these may influence inflammatory, metabolic, and clearance pathways implicated in Alzheimer's disease, though it has not been established that they remove tau pathology or replace disease-modifying treatment.
This is where nutritional therapy may have a supportive role, not as an alternative to medical care, but as a structured way of identifying and addressing potentially modifiable contributors to brain health. For one person that might mean correcting a B12 deficiency that has gone undetected for years. For another it could be blood sugar regulation, poor sleep, or cardiovascular risk. The point is that these things can be assessed and addressed in coordination with a person's medical team.
Multidomain programmes such as ReCODE attempt to bring these factors into a personalised framework. Evidence for ReCODE remains preliminary, and it should be regarded as an adjunct to appropriate medical care rather than a proven method of preventing, halting, or reversing Alzheimer's disease. A randomised controlled trial is currently underway (ClinicalTrials.gov, NCT04685590).
If you have noticed memory changes, discussing them with your general practitioner (GP) or an appropriate memory service is an important first step. People concerned about future risk can also review established modifiable risk factors with qualified health professionals. The science does not yet have all the answers. But there is more to do right now than most people realise, and none of it requires waiting for a drug that does not yet exist.
About Nicolle and You Nutrition Clinic
Nicolle is a memory clinic nurse, ReCODE-certified practitioner and registered nutritional therapy practitioner with a particular interest in cognitive health. She supports people living with Alzheimer’s disease and other forms of dementia, working alongside conventional medical care rather than replacing it.
Her personalised approach considers potentially modifiable aspects of health that may influence overall brain wellbeing. These can include nutritional status, metabolic and cardiovascular health, sleep, gut health and inflammatory processes.
Nicolle also works with people who have noticed changes in their memory or want to take a proactive approach to maintaining their cognitive health. Her practice extends to individuals living with epilepsy and those who have experienced a traumatic brain injury, where nutrition, metabolism and inflammation may also be relevant considerations.
Trained in the Bredesen Protocol and the ReCODE (Reversal of Cognitive Decline) framework, Nicolle draws upon current nutritional and pharmaceutical research to inform her work.
If you are ready to take a personalised, evidence-informed approach to your brain health, get in touch to find out how Nicolle can support you.
Email Nicolle at nicolle@younutritionclinic.com
Find out more about our services at younutritionclinic.com/cognitive-health
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Disclaimer: This article is for informational and educational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional for diagnosis and treatment decisions.
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