Dataset Information

Alzheimer's disease: experimental models and reality.

ABSTRACT: Experimental models of Alzheimer's disease (AD) are critical to gaining a better understanding of pathogenesis and to assess the potential of novel therapeutic approaches. The most commonly used experimental animal models are transgenic mice that overexpress human genes associated with familial AD (FAD) that result in the formation of amyloid plaques. However, AD is defined by the presence and interplay of both amyloid plaques and neurofibrillary tangle pathology. The track record of success in AD clinical trials thus far has been very poor. In part, this high failure rate has been related to the premature translation of highly successful results in animal models that mirror only limited aspects of AD pathology to humans. A greater understanding of the strengths and weakness of each of the various models and the use of more than one model to evaluate potential therapies would help enhance the success of therapy translation from preclinical studies to patients. In this review, we summarize the pathological features and limitations of the major experimental models of AD, including transgenic mice, transgenic rats, various physiological models of sporadic AD and in vitro human cell culture models.

SUBMITTER: Drummond E

PROVIDER: S-EPMC5253109 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alzheimer's disease: experimental models and reality.

Drummond Eleanor E Wisniewski Thomas T

Acta neuropathologica 20161226 2

Experimental models of Alzheimer's disease (AD) are critical to gaining a better understanding of pathogenesis and to assess the potential of novel therapeutic approaches. The most commonly used experimental animal models are transgenic mice that overexpress human genes associated with familial AD (FAD) that result in the formation of amyloid plaques. However, AD is defined by the presence and interplay of both amyloid plaques and neurofibrillary tangle pathology. The track record of success in ...[more]

PMID: 28025715

Similar Datasets

Project description:Parkinson's disease (PD) is a chronic, progressive movement disorder of adults and the second most common neurodegenerative disease after Alzheimer's disease. Neuropathologic diagnosis of PD requires moderate-to-marked neuronal loss in the ventrolateral substantia nigra pars compacta and ?-synuclein (?S) Lewy body pathology. Nigrostriatal dopaminergic neurodegeneration correlates with the Parkinsonian motor features, but involvement of other peripheral and central nervous system regions leads to a wide range of non-motor features. Nigrostriatal dopaminergic neurodegeneration is shared with other parkinsonian disorders, including some genetic forms of parkinsonism, but many of these disorders do not have Lewy bodies. An ideal animal model for PD, therefore, should exhibit age-dependent and progressive dopaminergic neurodegeneration, motor dysfunction, and abnormal ?S pathology. Rodent models of PD using genetic or toxin based strategies have been widely used in the past several decades to investigate the pathogenesis and therapeutics of PD, but few recapitulate all the major clinical and pathologic features of PD. It is likely that new strategies or better understanding of fundamental disease processes may facilitate development of better animal models. In this review, we highlight progress in generating rodent models of PD based on impairments of four major cellular functions: mitochondrial oxidative phosphorylation, autophagy-lysosomal metabolism, ubiquitin-proteasome protein degradation, and endoplasmic reticulum stress/unfolded protein response. We attempt to evaluate how impairment of these major cellular systems contribute to PD and how they can be exploited in rodent models. In addition, we review recent cell biological studies suggesting a link between ?S aggregation and impairment of nuclear membrane integrity, as observed during cellular models of apoptosis. We also briefly discuss the role of incompetent phagocytic clearance and how this may be a factor to consider in developing new rodent models of PD.

Dataset Information

Alzheimer's disease: experimental models and reality.

Publications

Alzheimer's disease: experimental models and reality.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets