Association of α-1-Antichymotrypsin Expression with the Development of Conformational Changes of Tau Protein in Alzheimer's Disease Brain

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023752%3A_____%2F23%3A43920804" target="_blank" >RIV/00023752:_____/23:43920804 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0306452222000021?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0306452222000021?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.neuroscience.2022.01.002" target="_blank" >10.1016/j.neuroscience.2022.01.002</a>

Result language

angličtina

Original language name

Association of α-1-Antichymotrypsin Expression with the Development of Conformational Changes of Tau Protein in Alzheimer's Disease Brain

Original language description

In Alzheimer&apos;s disease (AD), two mutually exclusive amino-terminal-dependent conformations have been reported to occur during the aggregation of Tau protein into neurofibrillary tangles (NFTs). An early conformation of full-length Tau, involving the bending of the amino terminus over the third repeated domain, is recognized by the Alz-50 antibody, followed by a second conformation recognized by Tau-66 antibody that depends on the folding of the proline-rich region over the third repeated domain in a molecule partially truncated at the amino- and carboxyl-termini. α-1-antichymotrypsin (ACT) is an acute phase serum glycoprotein that accumulates abnormally in the brain of AD patients, and since it is considered to promote the in vitro and in vivo aggregation of amyloid-β, we here seek further evidence that ACT may also contribute to the abnormal aggregation of Tau in AD. By analyzing brain samples from a population of AD cases under immunofluorescence and high-resolution confocal microscopy, we demonstrate here the abundant expression of ACT in hippocampal neurons, visualized as a granular diffuse accumulation, frequently reaching the nuclear compartment. In a significant number of these neurons, intracellular NFTs composed of abnormally phosphorylated and truncated Tau at Asp421 were also observed to coexist in separated regions of the cytoplasm. However, we found strong colocalization between ACT and diffuse aggregates of Tau-66-positive granules, which was not observed with Alz-50 antibody. These results suggest that ACT may play a role during the development of Tau conformational changes facilitating its aggregation during the formation of the neurofibrillary pathology in AD.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30210 - Clinical neurology

Project

—

Continuities

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Publication year

2023

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Neuroscience

ISSN

0306-4522

e-ISSN

1873-7544

Volume of the periodical

518

Issue of the periodical within the volume

May

Country of publishing house

GB - UNITED KINGDOM

Number of pages

18

Pages from-to

83-100

UT code for WoS article

000989824300001

EID of the result in the Scopus database

2-s2.0-85123357105