Alzheimer's Disease as a Membrane Dysfunction Tauopathy? New Insights into the Amyloid Cascade Hypothesis

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064173%3A_____%2F24%3A43927538" target="_blank" >RIV/00064173:_____/24:43927538 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/24:10484717 RIV/00216208:11120/24:43927538 RIV/00064190:_____/24:10001320 RIV/00064165:_____/24:10484717
Result on the web
<a href="https://doi.org/10.3390/ijms25179689" target="_blank" >https://doi.org/10.3390/ijms25179689</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ijms25179689" target="_blank" >10.3390/ijms25179689</a>

Result language
angličtina
Original language name
Alzheimer's Disease as a Membrane Dysfunction Tauopathy? New Insights into the Amyloid Cascade Hypothesis
Original language description
The amyloid cascade hypothesis postulates that extracellular deposits of amyloid β (Aβ) are the primary and initial cause leading to the full development of Alzheimer's disease (AD) with intracellular neurofibrillary tangles; however, the details of this mechanism have not been fully described until now. Our preliminary data, coming from our day-to-day neuropathology practice, show that the primary location of the hyperphosphorylated tau protein is in the vicinity of the cell membrane of dystrophic neurites. This observation inspired us to formulate a hypothesis that presumes an interaction between low-density lipoprotein receptor-related protein 1 (LRP1) and fibrillar aggregates of, particularly, Aβ(42) anchored at the periphery of neuritic plaques, making internalization of the LRP1-Aβ(42) complex infeasible and, thus, causing membrane dysfunction, leading to the tauopathy characterized by intracellular accumulation and hyperphosphorylation of the tau protein. Understanding AD as a membrane dysfunction tauopathy may draw attention to new treatment approaches not only targeting Aβ(42) production but also, perhaps paradoxically, preventing the formation of LRP1-Aβ(42).
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30109 - Pathology

Project
<a href="/en/project/NU23-04-00173" target="_blank" >NU23-04-00173: Utilization of RT-QuIC assay for improvement of diagnostics of neurodegenerative diseases: Prospective and retrospective studies</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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