After years of hits and misses trying to unlock the mysteries of Alzheimer’s disease, experts say recent research has yielded results that could reshape how doctors care for patients with the irreversible brain disorder that currently has no cure.
An experimental drug that targets a different brain protein than current treatments appeared to slow early stages of cognitive decline in patients, according to clinical trial results announced this week. The findings unlock the possibility of tackling Alzheimer’s from multiple angles.
Researchers are working to target the full “constellation” of processes that drive Alzheimer’s with the goal of being able to one day deliver individualized treatments, said Dr. Adam Boxer, a professor of memory and aging at the University of California San Francisco, who was not involved in the new trial.
“This is just the beginning,” Boxer said.
Targeting tau
There are two main brain proteins linked to Alzheimer’s: amyloid and tau.
Two drugs that have been approved for Alzheimer’s, including one from Cambridge-based Biogen, take aim at amyloid, the sticky protein that creates plaques in the brain. These therapies have shown modest benefits in slowing cognitive decline by reducing the buildup of amyloid.
Meanwhile, there is increased understanding of the role that tau, which forms tangles inside neurons, plays in driving the disease. But previous attempts to develop drugs targeting that protein have not been successful.
When amyloid builds up abnormally, it can trigger changes in tau, which eventually disrupts how neurons communicate with each other and leads to memory loss.
“For decades, there’s been the hypothesis that amyloid might be the match, but tau is really the fire that destroys the synapses and the neurons that cause the symptoms of Alzheimer’s disease,” Boxer said. “But that had never really been shown convincingly in living humans before.”
Now, Biogen says it’s making headway going after tau.
New results from a Phase 2 clinical trial of a therapy designed to stop the production of tau in the brain found the treatment not only lowered levels of the protein, but also appeared to slow early symptoms of Alzheimer’s. The findings were presented at the Alzheimer’s Association International Conference in London on Tuesday.
In one small group of the trial’s roughly 400 participants, people who received the drug — administered as a spinal shot twice a year — saw benefits that were comparable to the approved amyloid drugs.
The trial’s results are “really quite unprecedented with an anti-tau therapy,” said Dr. Priya Singhal, Biogen’s head of development. “A lot of work remains to be done, but we believe we have proof of concept in Phase 2.”
The study, which included people with early-stage Alzheimer’s, found that the lowest dose tested — 60 milligrams given once every six months — had the strongest effect. Compared to the placebo group, this dose was associated with a 26 percent reduction in cognitive decline. Experts said this was a surprising finding because the trial had the goal of demonstrating that higher doses lead to more benefits.
But Biogen researchers said the results still demonstrated meaningful clinical effects, and the company plans to launch a larger trial in 2027.
Other experts called the trial’s findings promising.
“Overall, they’re very encouraging,” Boxer said. “They’re like a double, like a second-base hit, not a home run.”
While the experimental drug showed some cognitive benefits, it didn’t appear to improve how people functioned, said Dr. Abhay Moghekar, a professor of neurology at Johns Hopkins University who was not involved in the trial.
“Ultimately, at the end of the day, no patient cares how well they did on a cognitive test,” Moghekar said. “They want to see, are they able to do things better?”
Side effects could also be a concern, said Dr. Daniel Press, an associate professor in neurology at Beth Israel Deaconess Medical Center and Harvard Medical School, who was not involved in the trial.
Reported side effects included pain at the location around the injection and temporary confusion, which could appear a few days after receiving the treatment and last about a week. But researchers noted there were no signs of brain inflammation, a side effect for some patients who’ve used the anti-amyloid drugs.
“These therapies absolutely positively work a little bit,” Press said. “I will die on the hill of fighting anyone who says they don’t work at all, and I will similarly say we have not cured Alzheimer’s.”
The future of treatment
Experts said the treatments, if used together along with others that are being developed, could yield greater benefits.
“It is likely that a cocktail of different treatments will be the most efficient,” said Li-Huei Tsai, a professor of neuroscience and director of the Picower Institute for Learning and Memory at MIT.
Researchers are studying whether combining tau therapies with anti-amyloid treatments can amplify their effects. Boxer is leading a trial to test drugs targeting both proteins in people with late-onset Alzheimer’s.
Beyond combining therapies, experts said it’s also critical to start diagnosing and treating people earlier.
“By the time somebody has symptoms, a lot of their synapses and neurons have already degenerated, and that’s why treating somebody who already has symptoms has not been as fruitful,” Moghekar said.
A new study conducted by researchers at Mass General Brigham found that a blood-based biomarker called p-tau217 could be useful in predicting the risk of Alzheimer’s in people without symptoms. Cognitively healthy people with very high levels of the biomarker, which can be tracked using a blood test, had a 38 percent risk of developing cognitive decline over the next five years, according to findings published in JAMA and presented at the Alzheimer’s conference in London on Wednesday.
“We’ve known for a while that amyloid is necessary but not sufficient” for Alzheimer’s to develop, said Dr. Reisa Sperling, the study’s senior author and a neurologist with the Mass General Brigham Neuroscience Institute. “This is telling us that there need to be changes in tau and at synapses for cognitive decline to manifest. But importantly, this happens early enough that we might be able to do something about it.”
But Sperling cautioned people from seeking a blood test for p-tau217 if they are cognitively healthy.
“People come into my office all the time asking for this test and if they are not cognitively impaired, I recommend against getting it,” she said. “It would not change what I tell that person in my office to do. They should still get plenty of exercise, sleep well, eat a heart-healthy diet, do all of the things whether they have a high p-tau217 or not.”
The biomarker could indicate that a person might respond to or need a treatment that targets amyloid and tau, she said.
“We don’t have that available for you today,” she said. “We hope to have it available sometime soon.”
Ongoing clinical trials are studying preventive treatments, such as giving a therapy to patients with early symptoms of Alzheimer’s. Another trial is studying the effects of an anti-amyloid therapy in cognitively healthy adults who have elevated levels of the protein in their brains.
If results from the preventive trials and research into combined therapies are positive, experts said, the future of treating Alzheimer’s could start to look more like how cancer patients receive care.
“We don’t wait until someone has metastatic disease, stage four cancer, and then treat them with one drug and see what happens,” Boxer said. “As soon as we know someone has cancer, we try to hit them with everything we have that’s really going to benefit them.”
Allyson Chiu can be reached at allyson.chiu@globe.com. Follow her on X @_allysonchiu.