Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by impairment of cognitive functions and memory loss. The two core neuropathological hallmarks of AD are deposits of beta-amyloid (A beta) fibrils in senile plaques and accumulation of hyperphosphorylated tau protein filaments in neurofibrillary tangles. An increasing number of murine models of AD have been generated. Animal models have been valuable tools for reproducing aspects of the neuropathological characteristics of AD strongly supporting the amyloid cascade hypothesis. However, we need to learn much more about the link between the pathological cascade of AD and the emergence of clinical symptoms to identify the factors which best predict the risk of progression from normal cognition to mild cognitive impairment and AD dementia. The few therapeutic agents currently available, such as galantamine, memantine, rivastigmine and donepezil are useful for symptomatic management and none of them is able to modify the disease progression. Studies with transgenic mouse models and data from clinical trials suggest that A beta-modifying therapies have no or limited effect after neuronal degeneration has begun, and stress the need of validated biomarkers for stratification of patients more responsive to immunotherapeutic agents. It is hoped that further efforts will move toward defining the preclinical stage of AD when intervention with anti-A beta immunotherapy may be most efficacious. The present paper reports a brief overview of AD and some murine models focusing on what we have learned from AD modeling

Alzheimer's disease murine models: focus on late-onset disease

Maria Assunta Potenza;Carmela Nacci;Maria Rosaria Carratù
2020

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by impairment of cognitive functions and memory loss. The two core neuropathological hallmarks of AD are deposits of beta-amyloid (A beta) fibrils in senile plaques and accumulation of hyperphosphorylated tau protein filaments in neurofibrillary tangles. An increasing number of murine models of AD have been generated. Animal models have been valuable tools for reproducing aspects of the neuropathological characteristics of AD strongly supporting the amyloid cascade hypothesis. However, we need to learn much more about the link between the pathological cascade of AD and the emergence of clinical symptoms to identify the factors which best predict the risk of progression from normal cognition to mild cognitive impairment and AD dementia. The few therapeutic agents currently available, such as galantamine, memantine, rivastigmine and donepezil are useful for symptomatic management and none of them is able to modify the disease progression. Studies with transgenic mouse models and data from clinical trials suggest that A beta-modifying therapies have no or limited effect after neuronal degeneration has begun, and stress the need of validated biomarkers for stratification of patients more responsive to immunotherapeutic agents. It is hoped that further efforts will move toward defining the preclinical stage of AD when intervention with anti-A beta immunotherapy may be most efficacious. The present paper reports a brief overview of AD and some murine models focusing on what we have learned from AD modeling
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/258153
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