Acta Neuropathologica: In-body amplification of pathogenic tau proteins retains disease-specific bioactive characteristics

The micro-tube-related protein tau (tau) has an insiditive disorder and a high degree of solubility when not binding to the micro-tube.
presence of excessive phosphate tau inclusions in the human brain is pathologically defined as a group of neurodegenerative diseases, collectively known as tau disease.
most common tau disease, Alzheimer's disease (AD), affects about 10 percent of the population over the age of 65.
in the brains of AD patients, cognitive decline and neuron death were closely associated with increased load on aggregation of taus, known as pairs of helixes (PHFs).
as the disease progresses, PHFs spread to the entire anatomically connected brain region.
this diffusion follows a pattern that begins in the limbic system and then spreads to the frontal temporal lobe and the new cortical layer.
recent studies have shown that tau strains exhibit strain-specific biological activity in tau propagation models, also known as pathogenicity.
currently, tau prefabribrised fibers (pffs) synthesized from recombinant tau proteins do not fully reproduce the specific pathogenicity of human-sourced tau strains.
but replicate disease-related tau pathology in cellular and animal models, which requires the use of tau from human brain sources.
, however, the availability of human-origin tau is extremely limited.
can simulate the production of pathogenic tau variants of human-sourced tau seeds will significantly expand the experimental design scale in the field of tau disease research.
previous studies have shown that in-in-body inoculation responses can amplification of the tau protein's β-folding structure from trace amounts of the man-sourced tau protein.
, however, whether the specific pathogenicity of strains of tau seeds from primitive human sources can be maintained in amplified tau strains remains to be tested.
this study used brain-based tau seeds rich in biomass from AD, cortical substrate degeneration (CBD) and active nuclear paralysis (PSP) patients, using improved inoculation programs to recombine 2N4R (T40) tau in introphy.
experiment used a recently developed tau diffusion model to quantitatively study the effectiveness of amplification reactions and the pathogenic fidelity of amplification substances to the original tau seeds.
study showed that tau isolated from different tau brains can faithfully expand different tau strains in-body, and that the amplified tau variant retains its strain-dependent pathogenic properties.
Xu, H., O’Reilly, M., Gibbons, G.S. et al. In vitro amplification of pathogenic tau conserves disease-specific bioactive characteristics. Acta Neuropathol 141, 193–215 (2021). MedSci Original Source: MedSci Original Copyright Notice: All text, images and audio and video materials on this website that indicate "Source: Mets Medicine" or "Source: MedSci Originals" are owned by Mets Medicine and are not authorized to be reproduced by any media, website or individual, and are authorized to be reproduced with the words "Source: Mets Medicine".
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