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Article Dans Une Revue Acta Neuropathologica Communications Année : 2023

Myelin in Alzheimer’s disease: culprit or bystander?

Résumé

Alzheimer's disease (AD) is a neurodegenerative disorder with neuronal and synaptic losses due to the accumulation of toxic amyloid β (Αβ) peptide oligomers, plaques, and tangles containing tau (tubulin-associated unit) protein. While familial AD is caused by specific mutations, the sporadic disease is more common and appears to result from a complex chronic brain neuroinflammation with mitochondriopathies, inducing free radicals' accumulation. In aged brain, mutations in DNA and several unfolded proteins participate in a chronic amyloidosis response with a toxic effect on myelin sheath and axons, leading to cognitive deficits and dementia. Αβ peptides are the most frequent form of toxic amyloid oligomers. Accumulations of misfolded proteins during several years alters different metabolic mechanisms, induce chronic inflammatory and immune responses with toxic consequences on neuronal cells. Myelin composition and architecture may appear to be an early target for the toxic activity of Aβ peptides and others hydrophobic misfolded proteins. In this work, we describe the possible role of early myelin alterations in the genesis of neuronal alterations and the onset of symptomatology. We propose that some pathophysiological and clinical forms of the disease may arise from structural and metabolic disorders in the processes of myelination/demyelination of brain regions where the accumulation of non-functional toxic proteins is important. In these forms, the primacy of the deleterious role of amyloid peptides would be a matter of questioning and the initiating role of neuropathology would be primarily the fact of dysmyelination.
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Dates et versions

hal-04054697 , version 1 (31-03-2023)

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Michel Maitre, Hélène Jeltsch-David, Nwife Getrude Okechukwu, Christian Klein, Christine Patte-Mensah, et al.. Myelin in Alzheimer’s disease: culprit or bystander?. Acta Neuropathologica Communications, 2023, ⟨10.1186/s40478-023-01554-5⟩. ⟨hal-04054697⟩
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