In Alzheimer's mice without the AD risk gene Abi3, fewer microglia crowd around amyloid plaques. Cultured microglia without Abi3 appear stuck in a torpor, even though their phagocytosis mostly works.
The new gene JADE1 encodes an adaptor protein that sits in tangles and nonetheless appears neuroprotective. The study also turned up three AD and two PSP genes, suggesting PART overlaps with these conditions.
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.
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.
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.
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.
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.
In human microglia-like cells, soluble CD22 stalled normal breakdown of fats. Blocking sCD22 greased the system, evoking a treatment for lysosomal-storage disorders.
Blood from fit mice reduced neuroinflammation in inactive mice. The can-do component? Clusterin, an apolipoprotein linked to Alzheimer’s. Clusterin tamped down interferon and cytokine signaling.
A repurposing study tapped sildenafil as an Alzheimer’s drug candidate. It suppresses p-tau in cultured neurons, men who take it are less prone to AD, and a trial is planned.
For amyloidogenic proteins such as Aβ and tau, third-party proteins bearing similar sequences sway aggregation kinetics. Does this underlie cells’ selective vulnerability to amyloid?
The EMA's decision was expected. Biogen announced it will appeal but also halved the drug's price. The company said it plans to complete a confirmatory trial by 2026.