Journal Article (Review Article)

DZNE-2021-00713

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neuronal Hyperexcitability in APPSWE/PS1dE9 Mouse Models of Alzheimer's Disease.

Müller, L. ; Kirschstein, T. ; Köhling, R. ; Kuhla, A. ; Teipel, S. (Last author)DZNE*

2021
IOS Press Amsterdam

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Please use a persistent id in citations: doi:10.3233/JAD-201540

Abstract: Transgenic mouse models serve a better understanding of Alzheimer's disease (AD) pathogenesis and its consequences on neuronal function. Well-known and broadly used AD models are APPswe/PS1dE9 mice, which are able to reproduce features of amyloid-β (Aβ) plaque formations as well as neuronal dysfunction as reflected in electrophysiological recordings of neuronal hyperexcitability. The most prominent findings include abnormal synaptic function and synaptic reorganization as well as changes in membrane threshold and spontaneous neuronal firing activities leading to generalized excitation-inhibition imbalances in larger neuronal circuits and networks. Importantly, these findings in APPswe/PS1dE9 mice are at least partly consistent with results of electrophysiological studies in humans with sporadic AD. This underscores the potential to transfer mechanistic insights into amyloid related neuronal dysfunction from animal models to humans. This is of high relevance for targeted downstream interventions into neuronal hyperexcitability, for example based on repurposing of existing antiepileptic drugs, as well as the use of combinations of imaging and electrophysiological readouts to monitor effects of upstream interventions into amyloid build-up and processing on neuronal function in animal models and human studies. This article gives an overview on the pathogenic and methodological basis for recording of neuronal hyperexcitability in AD mouse models and on key findings in APPswe/PS1dE9 mice. We point at several instances to the translational perspective into clinical intervention and observation studies in humans. We particularly focus on bi-directional relations between hyperexcitability and cerebral amyloidosis, including build-up as well as clearance of amyloid, possibly related to sleep and so called glymphatic system function.

Keyword(s): Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: physiopathology (MeSH) ; Amyloid beta-Protein Precursor: genetics (MeSH) ; Animals (MeSH) ; Disease Models, Animal (MeSH) ; Mice (MeSH) ; Neurons: physiology (MeSH) ; Presenilin-1: genetics (MeSH) ; APPswe/PS1dE9 mice ; Alzheimer’s disease ; amyloid-β ; neuronal hyperexcitability ; sleep-wake cycle

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Contributing Institute(s):

1. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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