Tau seeding dynamics in Alzheimer's disease
2018
Harvard Medical School, Charlestown, USA
Hyperphosphorylated tau aggregates in the form of neurofibrillary tangles are a hallmark of Alzheimer's disease. Many studies have suggested a "prion-like" behaviour of tau aggregates along neurons. In this study, different tools are used to analyse tau dynamics in human models of Alzheimer's disease. First, lysates of human brain areas with scarce neurofibrillary tangles were capable of inducing substantial tau seeding in a human tau biosensor cell line. Also, tau seeding was detected in areas of the human central nervous system affected by the pathology and the non-affected containing regions, and in areas that contain little to no neuronal cell bodies. This data suggested that pathogenic tau aggregates precede tau pathology with transneuronal spread through synapses, which was confirmed by the significant enrichment of seed competent tau in synaptosome fractions isolated from brains of varying Braak stages. This study provides evidence that tau pathology might be spread along the synaptic connections and linked to the extension of Alzheimer's pathogenesis in the human brain. Further investigation on this matter might bring new potential targets to stop the spread of the disease.
Synaptic tau seeding precedes tau pathology in human Alzheimer's disease brain
Bradley T Hyman
Added on: 08-16-2021
[1] https://www.frontiersin.org/articles/10.3389/fnins.2018.00267/full[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb
