Acta Neuropathologica: The maturation of neuron AD-tau pathology includes cytostyte and synth tau-specific phosphatization prior to compositional changes and formation of primary fibers

The two main pathological features of Alzheimer's disease (AD) are extracellular deposition of amyloid β protein (A beta) in intracellular tau protein aggregates and plaques present in the form of neurogenic fibrous tangles (NFTs).
A beta and tau are both transmitted in the brain along the path of neuroanatomy.
in AD, the tau protein underwent a multi-step process, from natural unfolded monosomes to large aggregate structures such as NFTs.
, however, it is not clear which events triggered the early preclinical stages of AD and whether they have an effect on the spread of tau pathology in the later stages of the disease.
to solve this problem, this paper analyzed the distribution of fibrous tau (Gallyas-tau) detected by T231, S396/S404 and S202/T205 phosphorylation, MC1 surface configuration modification, and Gallyas method in 15 patients with symptoms and 20 cases of asymptomatic AD patients, as well as 19 patients with non-AD.
As the initial tau damage, we found that phosphorylation T231-tau was widely distributed within the body myelin interval (IC tau), and phosphorylation S396/pS404 tau was distributed in white axon damage and neuropeptides (IN-tau).
pT231-tau subcellular positioning in the cell body and pS396/pS404-tau pre-synapse positioning were confirmed in hp301L mutant fruit fly larvae.
S202/T205-tau, MC1-tau, and Gallyas-tau were all negative for these lesions.
This study observed IC-tau and IN-tau in all analytical regions of the human brain, including the early-stage affected areas (inner olfactory cortology) in non-AD patients and the late-stage affected areas (the small brain) of symptomatic AD patients, suggesting that tau followed a similar process when it spread to previously unaffected areas.
addition, we have observed a series of AD-related tau aggregate maturation, first the emergence of IC-tau and IN-tau, then pT231 tau, pS396/pS404 tau and pS202/pT205 tau, followed by MC1 image tau, and finally the formation of Gallyas positive NFTs.
above, this study expands knowledge of the preclinical stages of AD, in particular the sequence of initial events that occur when tau aggregation is formed and the processes that occur when tau pathology spreads to unaffected brain regions.
Aragão Gomes, L., Uytterhoeven, V., Lopez-Sanmartin, D. et al. Maturation of neuronal AD-tau pathology involves site-specific phosphorylation of cytoplasmic and synaptic tau preceding conformational change and fibril formation. Acta Neuropathol 141, 173–192 (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 Original" 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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