Resumen de Patología sináptica y deterioro cognitivo en ratones que sobreexpresan distintas formas de la proteína humana precursora del beta-amiloide
Alzheimer's Disease is a neurodegenerative disorder associated with aging with two characteristic histophatological hallmarks: amyloid plaques, composed of the β-amyloid (Aβ) peptide, and intracellular neurofibrillary tangles, comprising aggregates of hyperphosphorilated tau. The neuronal loss and the early synaptic disfunction are the best correlate of cognitive decline in AD. Since Aβ was first identified as the main component of amyloid plaques, evidence has accumulated to suggest that this peptide is the primary neuropathological insult in AD according to the amyloid cascade hypothesis. However, there isn't a strong correlation between dementia and senile plaques but strong correlation have been observed with the number of tangles. Nonetheless, attention has turned towards soluble, oligomeric Aβ42, rather than insoluble forms. Recently some investigations have focused in the amyloid precursor protein (APP) providing evidence for a central role of this protein in the pathology. In this work APP processing, tau phosphorylation, neuronal integrity and synaptic function are examined in two transgenic mouse models overexpressing human APP with or without amyloidogenic mutations, by using biochemical and histological techniques.It is shown that overexpression of wild-type human APP induce the formation of toxic derivatives different from Aβ that leads to some of the main features of the AD as tau phosphorylation, synaptic disfunction and neuronal loss in brain structures related to memory. The elevated levels in Aβ42 peptide caused by the amyloidogenic mutations doesn't induce this disorders so that not only the Aβ peptide is crucial in the origin of AD but also the generation of other toxic derivatives caused by the APP overexpression.
