scholarly journals MicroRNAs and Alzheimer's Disease Mouse Models: Current Insights and Future Research Avenues

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Charlotte Delay ◽  
Sébastien S. Hébert
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Animal Models ◽  
Mouse Models ◽  
Future Research ◽  
Neuronal Function ◽  
Key Genes

Evidence from clinical trials as well as from studies performed in animal models suggest that both amyloid and tau pathologies function in concert with other factors to cause the severe neurodegeneration and dementia in Alzheimer’s disease (AD) patients. Accumulating data in the literature suggest that microRNAs (miRNAs) could be such factors. These conserved, small nonprotein-coding RNAs are essential for neuronal function and survival and have been implicated in the regulation of key genes involved in genetic and sporadic AD. The study of miRNA changes in AD mouse models provides an appealing approach to address the cause-consequence relationship between miRNA dysfunction and AD pathology in humans. Mouse models also provide attractive tools to validate miRNA targetsin vivoand provide unique platforms to study the role of specific miRNA-dependent gene pathways in disease. Finally, mouse models may be exploited for miRNA diagnostics in the fight against AD.

scholarly journals Rapamycin and Alzheimer’s disease: Time for a clinical trial?

2019 ◽  
Vol 11 (476) ◽  
pp. eaar4289 ◽  
Author(s):  
Matt Kaeberlein ◽  
Veronica Galvan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Animal Models ◽  
Mouse Models ◽  
Mtor Inhibitors ◽  
Beneficial Effects

The drug rapamycin has beneficial effects in a number of animal models of neurodegeneration and aging including mouse models of Alzheimer’s disease. Despite its compelling preclinical record, no clinical trials have tested rapamycin or other mTOR inhibitors in patients with Alzheimer’s disease. We argue that such clinical trials should be undertaken.

Neuronal Hyperexcitability in APPSWE/PS1dE9 Mouse Models of Alzheimer’s Disease

2021 ◽  
pp. 1-15
Author(s):  
Luisa Müller ◽  
Timo Kirschstein ◽  
Rüdiger Köhling ◽  
Angela Kuhla ◽  
Stefan Teipel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Models ◽  
Mouse Models ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Neuronal Firing ◽  
Neuronal Dysfunction ◽  
Neuronal Function ◽  
Neuronal Hyperexcitability

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.

scholarly journals Synaptic Loss in Alzheimer's Disease: Mechanistic Insights Provided by Two-Photon in vivo Imaging of Transgenic Mouse Models

2020 ◽  
Vol 14 ◽  
Author(s):  
Jaichandar Subramanian ◽  
Julie C. Savage ◽  
Marie-Ève Tremblay
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Models ◽  
Synaptic Loss ◽  
Two Photon ◽  
Synapse Loss ◽  
Disease Mutations ◽  
The Brain

Synapse loss is the strongest correlate for cognitive decline in Alzheimer's disease. The mechanisms underlying synapse loss have been extensively investigated using mouse models expressing genes with human familial Alzheimer's disease mutations. In this review, we summarize how multiphoton in vivo imaging has improved our understanding of synapse loss mechanisms associated with excessive amyloid in the living animal brain. We also discuss evidence obtained from these imaging studies for the role of cell-intrinsic calcium dyshomeostasis and cell-extrinsic activities of microglia, which are the immune cells of the brain, in mediating synapse loss.

scholarly journals Role of Endoplasmic Reticulum Stress in Learning and Memory Impairment and Alzheimer's Disease-Like Neuropathology in the PS19 and APPSwe Mouse Models of Tauopathy and Amyloidosis

eNeuro ◽  
2017 ◽  
Vol 4 (4) ◽  
pp. ENEURO.0025-17.2017 ◽  
Author(s):  
Denise Isabelle Briggs ◽  
Erwin Defensor ◽  
Pooneh Memar Ardestani ◽  
Bitna Yi ◽  
Michelle Halpain ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Learning And Memory ◽  
Mouse Models ◽  
Memory Impairment

scholarly journals The Role of the Innate Immune System in Alzheimer’s Disease and Frontotemporal Lobar Degeneration: An Eye on Microglia

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Elisa Ridolfi ◽  
Cinzia Barone ◽  
Elio Scarpini ◽  
Daniela Galimberti
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Lobar Degeneration ◽  
Environmental Changes ◽  
Current Evidence ◽  
Neuronal Function ◽  
Immune Effector ◽  
Effector Cells ◽  
The Central Nervous System

In the last few years, genetic and biomolecular mechanisms at the basis of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) have been unraveled. A key role is played by microglia, which represent the immune effector cells in the central nervous system (CNS). They are extremely sensitive to the environmental changes in the brain and are activated in response to several pathologic events within the CNS, including altered neuronal function, infection, injury, and inflammation. While short-term microglial activity has generally a neuroprotective role, chronic activation has been implicated in the pathogenesis of neurodegenerative disorders, including AD and FTLD. In this framework, the purpose of this review is to give an overview of clinical features, genetics, and novel discoveries on biomolecular pathogenic mechanisms at the basis of these two neurodegenerative diseases and to outline current evidence regarding the role played by activated microglia in their pathogenesis.

The role of EEG in clinical trials on Alzheimer's disease

2014 ◽  
Vol 35 ◽  
pp. S23
Author(s):  
Ilse van Straaten ◽  
P. Scheltens ◽  
C.J. Stam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials

Structural, Functional, and Molecular Neuroimaging Biomarkers for Alzheimer’s Disease

2013 ◽  
pp. 821-825
Author(s):  
James B. Brewer ◽  
Jorge Sepulcre ◽  
Keith A. Johnson
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cognitive Impairment ◽  
Neurodegenerative Disorders ◽  
Brain Dysfunction ◽  
Imaging Biomarkers ◽  
Neurocognitive Evaluation ◽  
Neuroimaging Biomarkers

Advances in quantitative structural, functional, and molecular neuroimaging have provided new tools for objective, in vivo, assessment of critical aspects of Alzheimer’s disease and other neurodegenerative disorders. Measures of brain atrophy or brain dysfunction, coupled with measures of disease-linked pathology, might complement the history, physical and neurocognitive evaluation of patients and thereby improve predictive prognosis, especially at early stages of cognitive impairment where neurodegenerative etiology is less certain. Such imaging biomarkers are currently used in nearly all clinical trials of therapeutic agents for Alzheimer’s disease and are increasingly incorporated into clinical practice. In this chapter, imaging biomarkers are introduced and discussed to familiarize the reader with their potential research and clinical uses.

Unraveling the Role of Mitochondria in Alzheimer’s Disease

2020 ◽  
pp. 407-430
Author(s):  
Sónia C. Correia ◽  
Paula I. Moreira ◽  
George Perry
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disease ◽  
Scientific Community ◽  
Future Research ◽  
Mitochondrial Bioenergetics ◽  
Limited Knowledge ◽  
Comprehensive Picture ◽  
Mitochondrial Defects

Alzheimer’s disease (AD) is an intriguing and still unsolved puzzle that has attracted, over the last decades, the interest of the scientific community. Despite the limited knowledge regarding the initial cause(s) of AD, mitochondrial abnormalities have been pinpointed as one of the earliest and strongest events related with the pathological course of this complex neurodegenerative disease. In this sense, the present chapter addresses three distinct but connected pieces of the AD puzzle: (a) how could defects of mitochondrial bioenergetics and dynamics contribute to AD pathology? (b) Could mitochondrial defects promote the disease-defining amyloid-β‎ and tau pathologies, and vice versa? and (c) Are mitochondria feasible therapeutic targets to postpone AD symptomatology and neuropathology, and, if so, how and when? The understanding and connection of these puzzle pieces provide a more comprehensive picture about the fundamental role of mitochondrial (mal)function in the neurodegenerative processes that occur in AD and propels future research interventions aimed to forestall AD-related pathological phenotype by bolstering mitochondrial “health.”

Learning from the Past: A Review of Clinical Trials Targeting Amyloid, Tau and Neuroinflammation in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 112-125 ◽  
Author(s):  
Kelly Ceyzériat ◽  
Thomas Zilli ◽  
Philippe Millet ◽  
Giovanni B. Frisoni ◽  
Valentina Garibotto ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Animal Models ◽  
Phase Iii ◽  
Current Status ◽  
Central Feature ◽  
Phase Iii Trial ◽  
The Past ◽  
Positive Results

Alzheimer’s Disease (AD) is the most common neurodegenerative disease and cause of dementia. Characterized by amyloid plaques and neurofibrillary tangles of hyperphosphorylated Tau, AD pathology has been intensively studied during the last century. After a long series of failed trials of drugs targeting amyloid or Tau deposits, currently, hope lies in the positive results of one Phase III trial, highly debated, and on other ongoing trials. In parallel, some approaches target neuroinflammation, another central feature of AD. Therapeutic strategies are initially evaluated on animal models, in which the various drugs have shown effects on the target (decreasing amyloid, Tau and neuroinflammation) and sometimes on cognitive impairment. However, it is important to keep in mind that rodent models have a less complex brain than humans and that the pathology is generally not fully represented. Although they are indispensable tools in the drug discovery process, results obtained from animal models must be viewed with caution. In this review, we focus on the current status of disease-modifying therapies targeting amyloid, Tau and neuroinflammation with particular attention on the discrepancy between positive preclinical results on animal models and failures in clinical trials.

scholarly journals In vivo testing of the role of Alzheimer’s disease coding variants

2020 ◽  
Vol 16 (S3) ◽  
Author(s):  
Michael Sasner ◽  
Adrian L. Oblak ◽  
Dylan Garceau ◽  
Kevin P. Kotredes ◽  
Christoph Preuss ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Vivo Testing ◽  
Coding Variants
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