At AAIC 2026 in London, tau modulation moved from a promising mechanism idea to a more validated therapeutic target. The July 12 T-PEP session showed how that drug development ecosystem is being built. The BIIB080 (diranersen) trial revealed cognitive benefit for a tau-targeting therapeutic. The LiBBY trial added an essential reminder: progress in dementia must include both disease-modifying science and effective, compassionate treatments for people living with advanced disease today. And much more…

The age of amyloid is joined by the time of tau

At the Alzheimer’s Association International Conference (AAIC) 2026 in London, the age of amyloid did not end; it was joined by the time of tau. That distinction matters. Amyloid-directed therapies have changed what is possible in Alzheimer’s disease (AD), but amyloid is only part of the biology. Tau pathology tracks closely with neuronal dysfunction and clinical decline in AD, and tau is the central pathology in more than 20 neurodegenerative diseases. In primary tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), there may be little or no amyloid pathology to target.

Across four days of presentations, AAIC 2026 showed that tau research is no longer organized around one therapeutic idea. Researchers are lowering MAPT expression, blocking the spread of tau seeds, restoring phosphatase activity, enhancing proteasomal clearance, degrading pathway regulators, strengthening cellular stress responses and building blood tests that may identify risk several years before symptoms begin.

The field is becoming more ambitious and precise, and independent coverage is capturing the shift. BioWorld centered its opening-day conference report on tau and the Rainwater Charitable Foundation’s (RCF) Sunday session, while STAT described tau as one of the meeting’s defining themes. That attention is an ecosystem milestone. The field is not simply producing more tau-centric ideas but improving how we measure and understand the results.  

Sunday put the pipeline at center stage

For the RCF, the conference’s defining moment came early. Sunday’s Featured Research Session, “Enabling the Tau Therapeutic Pipeline,” brought together a field-level pipeline update and four translational programs supported through the Tau Pipeline Enabling Program (T-PEP), a partnership between the RCF and the Alzheimer’s Association.

The response was immediate and encouraging. BioWorld’s same-day story positioned the session as evidence of the broader “time of tau.” Rather than focusing solely on late-stage clinical drugs, it highlighted the growing pipeline and the practical question at the heart of T-PEP: how do promising discoveries become investable, industry-ready programs?

The RCF’s own Glenn Harris, PhD, presented an updated landscape identifying 189 tau therapeutic programs through June 2026. Roughly four out of five remain in discovery or preclinical development, a sign of scientific momentum, but also a warning. Progress in the field will require more than new ideas; it needs the (often underfunded) work of lead optimization, in vivo validation, toxicology, biomarker development, manufacturing, and regulatory planning.

T-PEP was built for that translational purpose. Since the partnership began, the RCF and the Alzheimer’s Association have awarded more than $15 million across 23 grants. Dr. Harris reported that eight programs from the first four T-PEP classes have attracted venture capital funding, while two additional programs have been licensed or acquired. While those outcomes do not guarantee clinical success, they do show that focused philanthropy can help move scientifically compelling projects out of labs and closer to patients.

Four T-PEP programs showed the value of mechanistic diversity

The RCF believes that the measure of a translational program is whether the work creates a testable development candidate, a disease-relevant biomarker, an IND-ready package, or a credible handoff to the next source of funding and expertise.

The Sunday session was compelling because the talks attacked tau biology from four different directions rather than converging on a single mechanism.

• Timo Myohanen, PhD, University of Helsinki, Polku Therapeutics, presented POLK-38, a small molecule designed to activate protein phosphatase 2A (PP2A) through the PREP-PP2A interaction. PP2A is responsible for a large share of tau dephosphorylation and its activity is impaired in tauopathy brains. The program is testing whether restoring an endogenous protective pathway can rebalance tau biology rather than only bind an aggregate. POLK-38 reduced total and hyperphosphorylated tau in preclinical systems and produced encouraging behavioral signals in a tauopathy mouse model.
• Iryna Voytyuk, PhD, ALBORADA Drug Discovery Institute, described a viral vector strategy to activate the ubiquitin-independent 20S proteasome. Tau is an intrinsically disordered protein and can be cleared through this pathway without first being tagged with ubiquitin. By increasing 20S activity, the team aims to remove soluble tau monomer early and starve the nucleation step that precedes aggregation.
• Luc Buée, PhD, University of Lille, brought the discussion back to molecular specificity. His team is targeting PHF6, a six-amino-acid motif within tau’s microtubule-binding region, using single-domain antibody fragments. The lesson is straightforward but impactful: a tau therapy must be matched to the right isoform, conformation, compartment, and disease stage.
• Luana Fioriti, PhD, Mario Negri Institute, presented on a nanoparticle-carrying SUMO2-mimicking mRNA. Her group’s work suggests that chronic tau-related proteostatic stress can exhaust SUMO2-dependent resilience, contributing to synaptic loss and inflammation. In animal models and human-derived cells, the approach reduced synaptic loss and restored plasticity and memory. The program has now attracted additional U.S. Department of Defense support for toxicology, safety, and GMP manufacturing work.

Together, these presentations captured the central T-PEP thesis: a healthy tau pipeline must be biologically diverse, technically rigorous, and designed for translation.

Clinical tau programs supplied high-stake signals

On Monday, Eisai presented new data for etalanetug (E2814), an antibody directed at tau’s microtubule-binding region. In an open-label Phase 1b/2 study in dominantly inherited AD, etalanetug reduced CSF eMTBR-tau243, a biomarker associated with tau-tangle formation, by 62% at three months and 89% at nine months. Plasma eMTBR-tau243 fell by 78% and more than 90% at the same time points. CSF p-tau205, a later-stage tau-pathology marker, also declined.

The biomarker details were as important as the headline. Conventional plasma p-tau species increased after treatment, possibly due to antibody stabilized peripheral tau in the blood. eMTBR-tau243 also moved in the opposite direction, which is a reminder that a biomarker cannot be interpreted outside the mechanism of the drug being evaluated. The etalanetug result is not yet evidence of clinical benefit, but it may provide a cleaner pharmacodynamic tool for anti-tau antibodies.

Tuesday brought the most closely watched presentation: the Phase 2 CELIA study of diranersen, also known as BIIB080. Diranersen is an intrathecal antisense oligonucleotide that targets MAPT mRNA and lowers production of all tau isoforms. Across doses, CSF total tau fell 50% to 65%, and tau PET declined from baseline across evaluated brain regions. The 60 mg dose given every six months showed the strongest clinical pattern across several clinical rating scales.

The result deserves both excitement and discipline. CELIA missed its prespecified primary endpoint because higher doses did not produce greater observed clinical benefit. The study also did not separate from placebo on ADCS-ADL-MCI, a daily-function measure. The most responsible interpretation is that CELIA delivered encouraging Phase 2 proof of mechanism and a potentially important clinical signal that now must be replicated and explained in Phase 3. For PSP and other primary tauopathies, the data strengthens confidence that lowering tau in the human brain is pharmacologically achievable, but does not identify the optimal dose, stage, or disease-specific biomarker.

Delivery and targeted degradation broadened the definition of tau therapy

Voyager Therapeutics presented six-month nonhuman-primate data for VY1706, a one-time intravenous AAV gene therapy carrying a vectorized siRNA against MAPT. The program achieved up to 75% lowering of MAPT mRNA and tau protein in key brain regions through six months. Its capsid uses the endothelial receptor ALPL to cross the blood-brain barrier, and Voyager reported no adverse pathology through the highest tested dose. The FDA cleared the IND in June, with first dosing in early AD expected late 2026.

Denali’s DNL628, also known as OTV:MAPT, offered a different solution to the same delivery problem. The intravenous oligonucleotide uses a transferrin-receptor shuttle to cross the blood-brain barrier and distribute an ASO against MAPT. A Phase 1b study is testing the platform in patients with early AD.

Together, VY1706, DNL628, and intrathecal diranersen create a real-world experiment in how distribution, durability, reversibility, and treatment burden reduce tau.

Arvinas presented a PROTAC LRRK2 degrader that removed the entire LRRK2 protein rather than only inhibiting its kinase activity. In cells expressing human 0N4R tau and seeded with PSP patient-derived fibrils, the degrader reduced AT8-positive phospho-tau more strongly than two LRRK2 kinase inhibitors. A single oral dose also reduced soluble AT8 tau in PS19 mice. In nonhuman primates, LRRK2 degradation tracked with reductions in the lysosomal and inflammatory markers. These are preclinical tau data, not evidence that an LRRK2 degrader benefits people with PSP. However, the poster is strategically important. It connects a human genetic and biomarker signal in PSP with endolysosomal function, innate immune signaling, and pathological 4R tau. It also illustrates why targeted protein degradation may produce biology that conventional enzyme inhibition misses.

Blood biomarkers moved from detection toward staging and prognosis

On Wednesday, a large multi-cohort study moved plasma p-tau217 from diagnosis toward prognosis. Nearly 2,700 cognitively unimpaired adults were followed for a median 5.4 years, with some followed for more than a decade. People with very high p-tau217 had an estimated 38% risk of developing cognitive impairment within five years and 78% within 10 years. The practical opportunity is clear: lower-cost recruitment for prevention trials, earlier monitoring, and eventually more informed treatment decisions. Although p-tau217 is closely tied to AD amyloid and tau biology, it is not a validated blood test for PSP or CBD, and a risk estimate is not a deterministic prediction for an individual. In primary tauopathy cohorts, its near-term value may be to identify Alzheimer co-pathology rather than measure 4R tau itself.

Alamar Biosciences argued that the next step is multiplexing. Its NULISA presentations combined brain-derived p-tau217 and eMTBR-tau with more than 220 proteins related to inflammation, synaptic injury, neurodegeneration, and vascular biology. In a 300-person Korean cohort, the company reported that brain derived p-tau217 and eMTBR-tau were leading markers of amyloid positivity and tau-PET stage, with the combination improving discrimination relative to p-tau217 alone. Those results require independent validation, but the implication is compelling: one marker for an early amyloid-associated tau response, another for tangle formation, and additional proteins for the damage and cellular context around them.

LiBBY broadened the meaning of progress

Disease modification and dignity are not competing priorities. The RCF’s research program is centered on tau biology and therapies for PSP, CBD, AD, and related tauopathies. A complete translational ecosystem must also study symptom relief, caregiver burden, and quality of life across the full disease course including people with advanced dementia who have historically been excluded from trials.

One of the conference’s most important patient-care results was not tau-focused. The Phase 2 LiBBY trial tested a standardized oral combination of purified THC and CBD for clinically significant agitation in 120 people with dementia who were eligible for or receiving hospice care. LiBBY is not a disease-modifying study. It belongs to this report because it asked a question the field has too often neglected: can rigorous clinical research reduce suffering for people living with the most advanced stages of dementia?

The results from this rigorous study were encouraging. Within two weeks, patients taking the actual medication showed a clear drop in agitation compared to those on placebo—a benefit that lasted the full 12 weeks. Doctors reported that over 80% of treated patients showed noticeable overall improvement compared to a much smaller fraction of the placebo group. These results rely on a specific, research-grade formulated oil which delivered a precise daily dose of THC and CBD. While general side effects were similar between groups, serious medical events were higher in the medication group (23% vs. 12%). Researchers judged that none of these events were caused by the study drug itself. This is reassuring but doctors still urge caution until a full report details specific risks like falls or drug interactions.

The study’s design is a major achievement on its own. Most participants were around 80 years old, from an underrepresented ethnic group, and lived at home rather than in a facility. When the study was extended, patients continued to improve, and those who switched from the placebo to the real medication in the open-label extension saw benefits too.

LatAm-FINGERS: Brain-health strategies can travel when they are adapted, not copied

Progress in neurodegeneration requires both new treatments and practical delivery models that can reach the communities they are designed to serve.

The LatAm-FINGERS trial tested whether a structured lifestyle program could improve cognition in older adults at an elevated risk for dementia. The randomized study enrolled 1,065 people across 11 Latin American countries. Participants received guidance on exercise, nutrition, cognitive activity, social connection, and cardiovascular health, but the intensive group also received supervised exercise, computerized training, health monitoring, coaching, and regular group meetings.

After two years, the intensive group showed greater improvement in overall cognition than the comparison group, with additional gains in memory, executive function, and processing speed. The program was adapted to local communities, incorporating familiar foods, public spaces, and activities such as salsa and tango rather than applying a one-size-fits-all model.

The study did not prove that the program prevents dementia, and longer follow-up is needed to determine whether the cognitive gains last. Still, LatAm-FINGERS showed that brain-health interventions can work across diverse populations when they combine culturally relevant evidence-based guidance, coaching, and social support.

What the RCF takes from AAIC 2026

The most important tau story from London is that the field can now test multiple, mechanistically distinct tau hypotheses with increasingly informative biomarkers and sophisticated delivery systems. AAIC 2026 offered real reasons for optimism. The field is moving faster because it is becoming more rigorous and inclusive.

The RCF will continue to help build that rigor by tracking the pipeline, creating cross-discipline partnerships, funding high-value translational experiments, and insisting primary tauopathies remain part of the drug-development conversation. The time of tau will be meaningful only if it leads to treatments for people living with AD, PSP, CBD, and the many other disorders driven by pathological tau. And the broader field of dementia will be worthy of its ambition only if progress helps people at every stage. We hope to see you next year at AAIC 2027 in Chicago!