Seed-induced Aβ deposition alters neuronal function and impairs olfaction in a mouse model of Alzheimer’s disease

Abstract: Alzheimer’s disease (AD) is characterized by the accumulation of amyloid-β (Aβ) which ultimately forms plaques. These Aβ deposits can be induced in APP transgenic mouse models by prion-like seeding. It has been widely accepted that anosmia and hyposmia occur during the early stages of AD, even before cognitive deficits are present. In order to determine the impact of seed-induced Aβ deposits on olfaction, we performed intracerebral injections of seed-competent brain homogenate into the olfactory bulb of young pre-depositing APP transgenic mice. Remarkably, we observed a dramatic olfactory impairment in those mice. Furthermore, the number of newborn neurons as well as the activity of cells in the mitral cell layer was decreased. Notably, exposure to an enriched environment reduced Aβ seeding, vivified neurogenesis and most importantly reversed olfactory deficits. Based on our findings, we conclude that altered neuronal function as a result of induced Aβ pathology might contribute to olfactory dysfunction in AD

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Molecular psychiatry. - 27, 10 (2022) , 4274-4284, ISSN: 1476-5578

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2022

DOI
10.1038/s41380-022-01686-5
URN
urn:nbn:de:bsz:25-freidok-2286656
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:52 MEZ

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Entstanden

  • 2022

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