September 1st, 2026
Blood tests to assess Alzheimer's disease risk and progression exist, for example based on the presence of circulating varieties of tau protein, but there is a great deal of room for improvement. Researchers here provide evidence for an approach to the measurement of very small amounts of misfolded amyloid-β in blood to work reasonably well in patients. The amyloid cascade hypothesis continues to steer much of the field of research and development for Alzheimer's disease; misfolded amyloid-β spreads slowly in the brain over years, and eventually causes sufficient dysfunction to promote a subsequent disease stage characterized by a feedback loop between chronic inflammation and tau aggregation. Tracking this growth in misfolded amyloid-β make sense as an approach to assessing risk and progression of the early stages of Alzheimer's disease.
A hallmark of Alzheimer's disease (AD) pathophysiology is the misfolding and aggregation of β-amyloid (Aβ) protein in the brain, which results in tau pathology, neuroinflammation, synaptic loss, neurodegeneration, and cognitive decline. The misfolded Aβ aggregates, or "seeds", range from small, soluble oligomers to large, insoluble fibrils that have a rich β-sheet secondary structure and are generally stable. Because of its specific structure, Aβ seeds corrupt natively folded Aβ and promote the aggregation and formation of pathogenic assemblies, which is a process similar to prion-like aggregation. Such a process follows a secondary nucleation mechanism in which new aggregates generate at a rate dependent on the concentration of existing seeds.
