Suo, W.Z. GRK5KO Mouse Mirrors Mild Cognitive Impairment due to Alzheimer’s Disease. Preprints2024, 2024040829. https://doi.org/10.20944/preprints202404.0829.v1
APA Style
Suo, W.Z. (2024). GRK5KO Mouse Mirrors Mild Cognitive Impairment due to Alzheimer’s Disease. Preprints. https://doi.org/10.20944/preprints202404.0829.v1
Chicago/Turabian Style
Suo, W.Z. 2024 "GRK5KO Mouse Mirrors Mild Cognitive Impairment due to Alzheimer’s Disease" Preprints. https://doi.org/10.20944/preprints202404.0829.v1
Abstract
Alzheimer’s disease (AD) poses a significant public health challenge due to its irreversible and progressive nature while lack of a cure. As a potential strategy to combat AD, its prevention becomes increasingly attractive. Mild Cognitive Impairment due to AD (MCI-AD) represents a critical transitional stage between normal age-related cognitive decline and more severe AD conditions, occurring just before dementia onset. Unfortunately, there is currently no established animal model that accurately recapitulates MCI-AD characteristics. While many laboratories have traditionally used normally aged wild-type animals as experimental models, this approach falls short in representing the inherently worse state of MCI-AD compared to normal aging. To address this gap, we introduce an animal model—a transgenic mouse line with genetic inactivation of G protein-coupled receptor kinase-5 (GRK5), commonly known as the GRK5 knockout (GRK5KO) mouse. These GRK5KO mice exhibit amnesia, cognitive deficits, increased β-amyloid levels, neurofibrillary tangle (NFT) immunopositive axonopathy, and hippocampal neurodegenerative changes. Importantly, these pathological alterations predominantly impact the entorhinal, transentorhinal, and hippocampal cortices, aligning with human MCI-AD criteria and Braak stage II of human AD progression. Notably, female GRK5KO mice show approximately 2.5 times more NFT-positive axonopathy than males, mirroring the higher prevalence of AD cases in women. Collectively, existing data strongly supports the GRK5KO mouse as a qualified animal model for studying MCI-AD.
Keywords
Alzheimer’s disease; Mild cognitive impairment due to Alzheimer’s disease; aging; animal model; GRK5 deficiency; GRK5 knockout mouse.
Subject
Biology and Life Sciences, 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.
