By integrating plasma proteomics data from 35,000 Icelanders with data on disease-associated variations in their genomes, scientists cinched connections between gene variants that change protein levels in plasma, causing disease.
Transcriptomics pinpoints an expansion of pro-inflammatory microglia in people who carried the R47H-TREM2 variant. A similar cadre of microglia arose in female tauopathy mice carrying a single copy of the AD risk variant.
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.
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.
In a mouse model of amyloidosis, microglia carried Aβ aggregates into grafted wild-type tissue. The immune cells played a key part in the subsequent growth of plaques in the graft.
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.
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.
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.
Alzforum encourages users to visit the Virtual Exhibit Hall, where companies showcase their newest initiatives, products, and services. We welcome F. Hoffmann-La Roche, joining our other exhibitors — Biogen, BioLegend, Abcam, BrainXell, and the Jackson Laboratory.
In the largest plasma proteomic undertaking to date, researchers measured the concentration of thousands of proteins flowing in the blood of more than 35,000 Icelanders. When paired with these people's genetic sequences, more than 18,000 genetic variants correlated with protein levels. With GWAS data mixed in, links emerged between genetic variation, protein levels, and disease risk, allowing scientists to zero in on causal disease genes. One of them: TREM2.
APOE4-mediated Alzheimer’s risk may manifest in a person's 30s, according to a new proteomic study. Proteins upregulated in young carrier brains are part of an AD proteomic signature, though these proteins are downregulated in AD. Do they reflect early pathogenesis, then wane over time? Several of these proteins are targets of approved drugs, encouraging repurposing. One such drug, dasatinib, is already in AD clinical trials, highlighting the growing field of senolytics.
Microglia mean well, but sometimes their actions can do more harm than good. According to a new study, the cells can ingest and transport Aβ, setting off plaque growth in previously unaffected regions of the brain. The findings support growing evidence that microglia play a key part in plaque construction.
Lecanemab has made less of a splash than aducanumab or donanemab, but this anti-amyloid antibody appears to be building quiet momentum. At CTAD, researchers suggested an explanation for its lower incidence of the brain edema known as ARIA-E compared to other antibodies, and made a case for a consistent cognitive benefit in Phase 2. Lecanemab has been selected for the AHEAD 3-45 secondary prevention study and the DIAN-TU Tau Next Generation study; the latter will be the first test of amyloid and tau combination therapy.
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