For decades, Alzheimer’s research has focused heavily on beta-amyloid, a protein that forms sticky plaques between brain cells. That work has produced the first medications capable of modestly slowing the progression of early Alzheimer’s disease.
Scientists are now paying greater attention to another protein called tau. Unlike amyloid, tau accumulates inside neurons and forms twisted structures known as neurofibrillary tangles. The amount and location of abnormal tau appear to be closely associated with brain-cell damage, memory loss and the severity of Alzheimer’s symptoms.
Interest in tau increased further after an experimental drug called diranersen substantially lowered tau levels and showed possible signs of slowing cognitive decline in a mid-stage clinical trial. Although the results were mixed and the treatment remains years away from possible approval, the findings provide some of the strongest human evidence so far that directly targeting tau may alter the course of Alzheimer’s disease.
Healthy Brains Need Tau Protein
Tau is not naturally harmful. Every healthy brain contains it.
Neurons contain long internal structures called microtubules that help maintain cell shape and transport nutrients, proteins and other materials from one part of the cell to another. Tau binds to these microtubules and helps keep them stable.
In Alzheimer’s disease, chemical changes cause tau to detach from the microtubules. The protein begins misfolding and sticking to other tau molecules, eventually forming tangles inside the neuron. The cell’s internal transport system then becomes damaged, communication between neurons deteriorates and the affected cells may eventually die.
The US National Institute on Aging explains this process in its overview of what happens to the brain in Alzheimer’s disease. The disease does not create tau from nothing. It transforms a useful protein into a damaging form.
Tau May Track Symptoms More Closely Than Amyloid
Amyloid plaques can begin accumulating many years before memory problems become obvious. Some people have substantial amyloid deposits but relatively mild symptoms, particularly during the earliest stages of the disease.
Tau appears to provide a more direct picture of active neurodegeneration. As abnormal tau spreads from memory-related regions into wider areas of the brain, cognitive and functional difficulties generally become more severe.
Researchers quoted in AARP’s examination of tau and Alzheimer’s noted that abnormal tau is closely linked to neuron dysfunction and clinical symptoms. This relationship is one reason tau is becoming an important target for both diagnostic tests and potential treatments.
Amyloid may still play an essential role by initiating or accelerating the disease process. Tau, however, may be more closely connected to the damage that ultimately affects memory, language, decision-making and independence.
The Existing Alzheimer’s Drugs Target Amyloid
Lecanemab, sold as Leqembi, and donanemab, sold as Kisunla, are approved in the United States for certain patients with early Alzheimer’s disease. Both treatments are antibodies designed to remove forms of beta-amyloid from the brain.
Clinical trials showed that these medications can slow decline, but they do not stop or reverse Alzheimer’s. They also require careful patient selection and monitoring because they can cause amyloid-related imaging abnormalities, including brain swelling and small areas of bleeding.
The National Institute on Aging’s treatment guide explains that these medicines are intended for people in the mild cognitive impairment or mild dementia stages who have confirmed amyloid pathology.
Their limitations have strengthened the argument that Alzheimer’s may need to be treated through several biological pathways rather than through amyloid removal alone.
Diranersen Uses Gene-Silencing Technology
Diranersen, previously known as BIIB080, takes a very different approach from antibody treatments.
It is an antisense oligonucleotide, a short synthetic strand of genetic material designed to bind to the instructions cells use to produce tau. By interfering with those instructions, the drug reduces the production of tau protein.
The treatment is administered through an injection into the fluid surrounding the spinal cord. This delivery method helps it reach the central nervous system but is more invasive than an ordinary injection or tablet.
Biogen and Ionis Pharmaceuticals evaluated the drug in the 18-month CELIA Phase 2 study involving 416 people with early Alzheimer’s disease. Participants received one of three dosing schedules or a placebo. Details of the study design are recorded in the official ClinicalTrials.gov entry for CELIA.
The Drug Reduced Tau by as Much as 65%
Diranersen produced a clear biological effect.
Biogen reported average reductions of approximately 50% to 65% in total tau measured through spinal fluid and brain imaging. The decreases were maintained throughout the treatment period, indicating that the drug successfully reached its intended target.
Participants receiving the lowest tested dose, 60 milligrams once every six months, declined 26% more slowly than the placebo group on the Clinical Dementia Rating–Sum of Boxes scale. Benefits were also reported across several other measurements of memory, thinking and daily functioning.
Biogen presented the detailed findings at the 2026 Alzheimer’s Association International Conference. The company’s official CELIA results announcement described diranersen as the first tau-directed therapy to demonstrate substantial tau reduction alongside potential cognitive benefit in a randomised mid-stage study.
The Results Were Promising but Not Conclusive
The study did not achieve its main objective.
Researchers expected higher doses to produce progressively greater slowing of cognitive decline. Instead, the strongest clinical result appeared in the lowest-dose group. The higher-dose groups reduced tau but did not deliver a correspondingly larger cognitive benefit.
Because the study failed to demonstrate the planned dose-response relationship, the findings cannot yet prove that diranersen is effective. Smaller participant groups, statistical variation or an unexpected biological effect of lowering normal tau too aggressively could help explain the pattern.
Independent experts nevertheless described the results as important proof of principle. Reuters reported that the lowest dose showed improvement across five of six cognitive assessments, while reductions in tau were observed across all doses. Biogen plans to test the treatment in a much larger Phase 3 study.
The distinction matters. Diranersen is not an approved treatment, and the Phase 2 findings should not be interpreted as evidence that Alzheimer’s can currently be treated by reducing tau outside a clinical trial.
Targeting Tau Presents Difficult Technical Challenges
Amyloid plaques form outside brain cells, where antibodies can more easily reach them. Tau tangles develop inside neurons, making them harder for many medicines to access.
Tau also has a normal biological function. A treatment must reduce the harmful forms or lower total production enough to affect the disease without interfering excessively with the protein’s healthy role.
Previous tau-targeted drugs have included antibodies, vaccines, aggregation inhibitors and treatments intended to block the protein’s spread. Many failed to demonstrate meaningful clinical benefits.
Diranersen may have performed differently because it reduces the production of tau rather than attempting to remove tangles after they have already formed. That strategy could limit the supply of protein available to misfold, accumulate and move through the brain.
The spinal-injection method remains a practical disadvantage. Patients may need repeated lumbar punctures over many years, and a future trial must establish whether the potential benefit justifies that burden.
Tau Is Also Becoming an Important Diagnostic Marker
Researchers are not only targeting tau with medicines. They are also measuring it to detect and monitor Alzheimer’s.
Tau PET scans can reveal where abnormal tau has accumulated in the brain. Spinal-fluid testing can measure several tau-related biomarkers, while newer blood tests can detect phosphorylated forms such as p-tau217.
These biomarkers can help distinguish Alzheimer’s from other causes of cognitive decline and identify biological changes before severe dementia develops. The National Institute on Aging’s biomarker guide explains how tau imaging and laboratory tests may support diagnosis and disease monitoring.
More accessible testing could also improve clinical trials by helping researchers enrol participants at the stage when tau-targeted treatment is most likely to work.
Combination Treatment May Offer the Greatest Benefit
Alzheimer’s is unlikely to have a single biological cause. Amyloid, tau, inflammation, vascular damage, immune activity and genetic risk can all influence how the disease begins and progresses.
Future treatment may therefore resemble cancer or cardiovascular care, where several therapies are combined to address different parts of the illness.
An amyloid-removing medicine could reduce an early trigger, while a tau-targeting treatment could slow the damage spreading through neurons. Other drugs might control inflammation, protect synapses or improve the brain’s ability to clear harmful proteins.
The National Institute on Aging is already supporting research that combines amyloid treatment with experimental therapies intended to address tau. Its dementia treatment research overview describes combination studies as an important direction for the field.
Tau Could Change Alzheimer’s Treatment, but More Evidence Is Needed
The diranersen trial has not produced a cure, and it has not established that lowering tau will work reliably for patients. Its failure to meet the primary endpoint means the larger Phase 3 trial will be essential.
Even so, the study represents an important scientific step. It showed that researchers can substantially reduce tau inside the human brain and produced signs that doing so may slow cognitive decline.
For families affected by Alzheimer’s, the development offers cautious hope rather than an immediate treatment option. Current medical care should continue to be guided by qualified clinicians, approved therapies and individual health circumstances.
Tau may eventually become one of the most important targets in Alzheimer’s medicine. The decisive question is whether the biological success seen in early research can be converted into a safe, repeatable and clinically meaningful benefit for patients.
