Cholinergic neurodegeneration in Alzheimer disease mouse models

Shekari, Arman; Fahnestock, Margaret

doi:10.1016/b978-0-12-819973-2.00013-7

Cited by 18 publications

(13 citation statements)

References 155 publications

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“…Cholinergic signaling is essential for cognitive function. Basal forebrain is the primary output site of cholinergic energy in the central nervous system [ 28 ]. The central cholinergic circuit is involved in maintaining normal cognitive function and regulating signal transduction throughout the cerebral cortex.…”

Section: Physiological Function Of Cholinergic Systemmentioning

confidence: 99%

Role of Cholinergic Signaling in Alzheimer’s Disease

et al. 2022

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Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer’s disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.

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Section: Physiological Function Of Cholinergic Systemmentioning

confidence: 99%

Role of Cholinergic Signaling in Alzheimer’s Disease

et al. 2022

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“…Basal forebrain cholinergic neurons (BFCN) experience early and substantial degeneration in AD, with the major neurodegenerative correlate being accumulation of pTau in neurofibrillary tangles (Geula et al, 2021). Consequently, BFCN degeneration is regarded as one of the hallmarks of AD (Shekari and Fahnestock, 2021). (Chen and Mobley, 2019)with evidence of decreased BFB volume before Aβ cortical spreading (Lozano-Montes et al, 2020, Nair et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Early altered directionality of resting brain network state transitions in the TgF344-AD rat model of Alzheimer’s disease

De Waegenaere,

van den Berg,

Keliris

et al. 2024

Preprint

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Alzheimer’s disease (AD) is a progressive neurodegenerative disease resulting in memory loss and cognitive decline. Synaptic dysfunction is an early hallmark of the disease whose effects on whole-brain functional architecture can be identified using resting-state functional MRI (rsfMRI). Insights into mechanisms of early, whole-brain network alterations can help our understanding of the functional impact of AD’s pathophysiology. Here, we obtained rsfMRI data in the TgF344-AD rat model at the pre- and early-plaque stages. This model recapitulates the major pathological and behavioural hallmarks of AD. We used co-activation pattern (CAP) analysis to investigate if and how the dynamic organization of intrinsic brain functional networks states, undetectable by earlier methods, is altered at these early stages. We identified and characterized six intrinsic brain states as CAPs, their spatial and temporal features, and the transitions between the different states. At the pre-plaque stage, the TgF344-AD rats showed reduced co-activation of hub regions in the CAPs corresponding to the default mode-like and lateral cortical network. Default mode-like network activity segregated into two distinct brain states, with one state characterised by high co-activation of the basal forebrain. This basal forebrain co-activation was reduced in TgF344-AD animals mainly at the pre-plaque stage. Brain state transition probabilities were altered at the pre-plaque stage between states involving the default mode-like network, lateral cortical network, and basal forebrain regions. Additionally, while the directionality preference in the network-state transitions observed in the wild-type animals at the pre-plaque stage had diminished at the early-plaque stage, TgF344-AD animals continued to show directionality preference at both stages. Our study enhances the understanding of intrinsic brain state dynamics and how they are impacted at the early stages of AD, providing a nuanced characterization of the early, functional impact of the disease’s neurodegenerative process.

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“…Besides the absence of a widespread cell loss, Tg2576 mice did not show any build-up of neurofibrillary tangles either [ 27 ]. In general, the Tg2576 mouse model is considered as a modest neurodegenerative model possibly due to the promoter used in over-expressing APP [ 28 ]. This model was noted with high lethality in certain genetic backgrounds and males tended to be aggressive that required single housing [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Updates on mouse models of Alzheimer’s disease

Zhong,

Peng,

Duarte

et al. 2024

Mol Neurodegeneration

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Alzheimer’s disease (AD) is the most common neurodegenerative disease in the United States (US). Animal models, specifically mouse models have been developed to better elucidate disease mechanisms and test therapeutic strategies for AD. A large portion of effort in the field was focused on developing transgenic (Tg) mouse models through over-expression of genetic mutations associated with familial AD (FAD) patients. Newer generations of mouse models through knock-in (KI)/knock-out (KO) or CRISPR gene editing technologies, have been developed for both familial and sporadic AD risk genes with the hope to more accurately model proteinopathies without over-expression of human AD genes in mouse brains. In this review, we summarized the phenotypes of a few commonly used as well as newly developed mouse models in translational research laboratories including the presence or absence of key pathological features of AD such as amyloid and tau pathology, synaptic and neuronal degeneration as well as cognitive and behavior deficits. In addition, advantages and limitations of these AD mouse models have been elaborated along with discussions of any sex-specific features. More importantly, the omics data from available AD mouse models have been analyzed to categorize molecular signatures of each model reminiscent of human AD brain changes, with the hope to guide future selection of most suitable models for specific research questions to be addressed in the AD field.

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Cholinergic neurodegeneration in Alzheimer disease mouse models

Cited by 18 publications

References 155 publications

Role of Cholinergic Signaling in Alzheimer’s Disease

Role of Cholinergic Signaling in Alzheimer’s Disease

Early altered directionality of resting brain network state transitions in the TgF344-AD rat model of Alzheimer’s disease

Updates on mouse models of Alzheimer’s disease

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