Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Switching On/Off Amyloid Plaque Formation in Transgenic Animal Models of Alzheimer’s Disease

Version 1 : Received: 11 December 2023 / Approved: 12 December 2023 / Online: 15 December 2023 (12:23:06 CET)

A peer-reviewed article of this Preprint also exists.

Kozin, S.A.; Kechko, O.I.; Adzhubei, A.A.; Makarov, A.A.; Mitkevich, V.A. Switching On/Off Amyloid Plaque Formation in Transgenic Animal Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2024, 25, 72. Kozin, S.A.; Kechko, O.I.; Adzhubei, A.A.; Makarov, A.A.; Mitkevich, V.A. Switching On/Off Amyloid Plaque Formation in Transgenic Animal Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2024, 25, 72.

Abstract

A hallmark of Alzheimer’s disease (AD) are the proteinaceous aggregates formed by the amyloid-beta peptide (Aβ) that is deposited inside the brain as amyloid plaques. The accumulation of aggregated Aβ may initiate or enhance pathologic processes in AD. According to the amyloid hypothesis any agent that has the capability to inhibit Aβ aggregation and/or destroy amyloid plaques represents a potential disease modifying drug. In 2023, a humanized IgG1 monoclonal antibody (lecanemab) against the Aβ soluble protofibrils was approved by US FDA for AD therapy thus providing compelling support to the amyloid hypothesis. To acquire a deeper insight on the in vivo Aβ aggregation, various animal models, including aged herbivores and carnivores, non-human primates, transgenic rodents, fish and worms are widely exploited. This review is based on the recent data obtained using transgenic animal AD models and presents experimental verification of the critical role in Aβ aggregation seeding of the interactions between zinc ions, Aβ with the isomerized Asp7 (isoD7- Aβ) and the α4β2 nicotinic acetylcholine receptor.

Keywords

Alzheimer’s disease; transgenic animal model; amyloidogenesis; amyloid-beta; peptide; isoaspartate; zinc; α4β2 nicotinic acetylcholine receptor; aggregation seeding; anti-amyloid drug

Subject

Biology and Life Sciences, Neuroscience and Neurology

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