科研之友
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摘要
The aim of this study was to elucidate the molecular signature of Alzheimer's disease-associated amyloid pathology. We used the double APP(swe)/PS1(Delta E9) mouse, a widely used model of cerebral amyloidosis, to compare changes in proteome, including global phosphorylation and sialylated N-linked glycosylation patterns, pathway-focused transcriptome and neurological disease-associated miRNAome with age-matched controls in neocortex, hippocampus, olfactory bulb and brainstem. We report that signalling pathways related to synaptic functions associated with dendritic spine morphology, neurite outgrowth, long-term potentiation, CREB signalling and cytoskeletal dynamics were altered in 12 month old APP(swe)/PS1(Delta E9) mice, particularly in the neocortex and olfactory bulb. This was associated with cerebral amyloidosis as well as formation of argyrophilic tangle-like structures and microglial clustering in all brain regions, except for brainstem. These responses may be epigenetically modulated by the interaction with a number of miRNAs regulating spine restructuring, A beta expression and neuroinflammation. We suggest that these changes could be associated with development of cognitive dysfunction in early disease states in patients with Alzheimer's disease.
- 出版日期2016-6-7
