A Glimpse of the Future from the Alzheimer’s Association International Conference

Last week, over 11,000 experts gathered in London for the Alzheimer’s Association International Conference (AAIC). While data from promising Phase 2 trials and Alzheimer’s blood tests dominated the headlines, the week featured other advances that progress treatment and care for the disease. Here are some of the important trends that caught our eye.  

Tau trials and diagnostics

While beta-amyloid plaques are the target of two FDA-approved Alzheimer’s drugs, tau tangles, which form inside brain cells, correlate more closely with cognitive decline and disease progression. Until now, tau-targeting therapies like Johnson & Johnson’s posdinemab and Eli Lilly’s ceperognastat were discontinued after failing in Phase 2 trials, despite lowering tau. 

Dr. Marwan Sabbagh, a neurologist at Barrow Neurological Institute, told Being Patient that the field is “still struggling” to develop working tau drugs. 

But Biogen proved it’s possible for tau therapies to push past the Phase 2 plateau with diranersen, the first tau-targeting Alzheimer’s therapy to head to Phase 3 trials. Despite a negative trial which failed to find a dose-response relationship, the trial found the drug may slow decline and reduce tau levels, warranting further research, according to data presented at AAIC. 

Alamar Biosciences also announced the first blood test that provides a proxy measure of tau tangles. Existing tests, even those that measure fragments of tau like pTau-217, are more reflective of beta-amyloid plaques rather than tau tangles. The company’s test, which measures eMTBR-tau, finally allows researchers to measure tangles without requiring a lumbar puncture or expensive brain scan.

Steve Williams, chief scientific officer of Alamar Sciences, told Being Patient that the test can pick up tangles before the onset of symptoms. The blood test may “enable better recruitment in clinical trials and ultimately better clinical management.” 

The evolution of lifestyle prevention trials

Last year, the POINTER trial showed that a structured lifestyle intervention — including dietary changes, exercise, and coaching — resulted in slightly more cognitive improvement than an unstructured intervention over two years. 

This year, researchers at AAIC shared similar results from a trial across 11 Latin American countries. It isn’t clear what’s driving the small changes seen across the studies — some researchers question whether such lifestyle trials convincingly show success. If the difference between the two groups is due to practice effects, where people simply get better at cognitive questionnaires because they’re doing them a few times over the course of the study.

Still, the data these studies provide could be valuable. Arvid Gollwitzer, researcher at the Broad Institute, told Being Patient that AI models from data collected in these lifestyle trials could enable scientists to figure out who benefits most from these interventions. Analyzing the data that comes out of these trials, said Gollwitzer, could help scientists develop “counterintuitive ideas” and figure out new biomarkers to test out in the future. 

The Alzheimer’s Association announced that they will fund a $100 million trial combining lifestyle intervention with a GLP-1 drug to see if it could prevent dementia. Two massive trials conducted by Novo Nordisk testing their weight-loss blockbuster drug semaglutide found no benefit in slowing cognitive decline in early Alzheimer’s, but some researchers still think it may prevent dementia. 

Brown University epidemiologist Sarah Ackley said that while investigating GLP-1 drugs as Alzheimer’s prevention is worthwhile, interventions that test multiple lifestyle changes at once are intensive and can be costly to implement in the real world. Studies like these that combine multiple interventions  also make it difficult to understand why treatments work if the trial is positive, she said. 

Moving beyond Alzheimer’s

Alzheimer’s is the most common form of dementia, accounting for 70 percent of all cases. 

But the conference also prominently featured research into other causes of dementia, like limbic-predominant Age-related TDP-43 Encephalopathy (LATE), frontotemporal dementia, and dementia with Lewy bodies. Some talks focused on teasing apart mixed dementia, a common condition where individuals have multiple forms of the disease. There’s also cross-pollination in drug testing, in which treatments that have been tested trials for one form of dementia, like frontotemporal dementia, are occasionally tested for Alzheimer’s.

What’s happening next?

While making anti-amyloid drugs better and bringing anti-tau therapies to market are priorities, researchers are still trying to figure out ways to tackle neuroinflammation. “People recognize there’s a gap,” said Sabbagh. “We’re still waiting to see some good progress there as well.” 

He’s also interested in the potential of anti-cancer drugs, six of which are in trials to treatAlzheimer’s. At the conference, he presented very early human trials of one of these, lenalidomide.

Beyond that, the conference also highlighted a handful of important Phase 3 trials could enable the approval of new treatments and may release data before the end of the year. 

AriBio will present data from its trial of AR1001, a repurposed erectile dysfunction pill, at a November conference. Data from Cognito Therapeutics’ brain stimulation device SPECTRIS and Bristol-Myers Squibb’s agitation and psychosis drug KarXT Phase 3 trials will be released this year. 

If any of these trials succeed, it would mean more options for people with Alzheimer’s and their caregivers.