engleski

Experimental approach to Alzheimer's disease

This review on current experimental models of Alzheimer disease is based on human postmortem findings showing keystone markers for a pathology within the s-amyloid transduction cascade as well as pathology in the mechanism of phosphorylation of τau protein. Evidence for risk factors triggering this devastating disease focuses on type II diabetes. Therefore, modeling Alzheimer disease tries to get profound knowledge of these underlying mechanisms by studying experimental animal models. Here will be discussed in detail two pharmacological models, the one mirroring type II diabetes induced AD pathology by streptozotocin and its influences on the insulin/insulin receptor cascade as well as s-amyloid and τau pathologies. Behavioral studies give evidence that this model is currently the most detailed described AD model. While transgenic mouse models, like the APP Tg2576 model, demonstrate s-amyloid plaque formation and impaired memory rather in old age, streptozotocin is able to aggravate the process of pathology so that AD pathology is seen months earlier. This indicates a profound interaction of AD pathology with the insulin/insulin receptor cascade and pathobiochemistry. Modelling cholinergic deficits has been done by using the cholinotoxin AF64A. This model reflects changes in the acetylcholine metabolism as well as in monoaminergic transmitter systems, and behavioral studies are in line with AD-based impairment of learning and memory. However, s-amyloid and τau pathologies as well as insulin-resistant brain state have not been studied in detail.

AF64A model, Alzheimer disease, dementia model, streptozotocin, transgenic dementia models, type II diabetes

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