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The Role of Tau Pathology in Alzheimer’s Disease and Down Syndrome
Version 1
: Received: 24 January 2024 / Approved: 25 January 2024 / Online: 25 January 2024 (12:11:32 CET)
A peer-reviewed article of this Preprint also exists.
Granholm, A.-C.; Hamlett, E.D. The Role of Tau Pathology in Alzheimer’s Disease and Down Syndrome. J. Clin. Med. 2024, 13, 1338. Granholm, A.-C.; Hamlett, E.D. The Role of Tau Pathology in Alzheimer’s Disease and Down Syndrome. J. Clin. Med. 2024, 13, 1338.
Abstract
. The Tau protein is associated with microtubule function in the neuron and is crucial for normal axonal transport. In several different neurodegenerative disorders, Tau misfolding leads to hyper-phosphorylation (p-Tau) and intracellular p-Tau aggregates known as neurofibrillary tangles (NFTs). This is particularly evident in individuals with Down syndrome (DS), who develop Alzheimer’s disease-like (AD) neuropathology early in life with almost complete penetrance, associated with the development of dementia symptoms in their 40s or 50s. Our previous findings have shown that certain forms of p-Tau are present already in childhood in individuals with DS in neuron-derived exosomes, suggesting an early phosphorylation profile in this population that could influence the development of AD pathology. Misfolded p-Tau isoforms are known to be seeding competent and may be responsible for spreading AD pathology in different regions of the brain. This review is focused on the accumulation of p-Tau in the brain of individuals with DS and potential consequences for brain function.
Keywords
Down syndrome (DS); Alzheimer’s disease (AD); neurofibrillary tangles (NFTs); seeding competent p-Tau; neuropathology.
Subject
Medicine and Pharmacology, Neuroscience and Neurology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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