The 14th CTAD conference returned to Boston as a hybrid meeting, reuniting colleagues long separated by COVID, while also streaming most of the scientific program to viewers around the world. The conference featured morsels of news in the effort to move anti-amyloid antibodies past imbursement barriers at the CMS, and through the approval process at the FDA, respectively. Tau antibodies mostly came up short again, and a platform trial is forming to take on this complex target more systematically. Plasma biomarkers continued their rapid advance. Digital versions of known and new cognitive tests drew note, as did AI-based projects to detect subtle changes in a person’s speech.
While a death causes jitters, new blood phospho-tau data from Phase 3 trials strengthen the antibody’s claim to disease modification, and post-market studies seek evidence of benefit.
At CTAD, all eyes were on the anti-amyloid antibody donanemab, which is before the FDA. Scientists showed how Phase 3 is enrolling, and how plasma tau enables wholly remote inclusion of people with plaques and tangles.
Data shown at CTAD suggests the Aβ42/40 ratio falls in the blood before it does in the CSF, offering perhaps the earliest glimpse at the pathophysiology of Alzheimer's. Measuring that change prospectively might be a tall order.
At CTAD, scientists discussed whether a cognitive benefit on semorinemab was real, even as gosuranemab might have made people a bit worse. Other scientists are building an ambitious tau platform, including combination trials.
In a comparison with aducanumab and gantenerumab, lecanemab mopped up protofibrils most efficiently; the antibody has been chosen for DIAN-TU and AHEAD 3-45 trials.
While Phase 3 trials of subcutaneous gantenerumab continue, scientists say delivering the antibody to the brain via the transferrin receptor might be twice as efficient.
The same 24 proteins that are downregulated in an Alzheimer’s proteomic study are turned up in young APOE4 carriers. Two proteins, the kinases Yes1 and Fyn1, are targets of the drug dasatinib, which is being tested as an anti-aging senolytic in AD.
AI-powered apps catch changes in how a person speaks that may reveal cognitive decline in frontotemporal dementia and early Alzheimer’s. Can smartphones deliver biomarkers for trial enrollment and diagnosis?
At CTAD, scientists presented an electronic version of the CDR, plus new digital tests. Will smartphone apps pick up mild cognitive impairment and even preclinical cognitive change?