Neurodegenerative Alzheimer-like Pathology in PDAPP 717V → F Transgenic Mice

Autor: Dora Games, Eliezer Masliah, Henry Grajeda, Karen S. Chen, Ruth Motter, Terry Guido, J Huang, F Soriano, Karen Khan
Rok vydání: 1997
Předmět:
Zdroj: Connections, Cognition and Alzheimer’s Disease ISBN: 9783642645044
Popis: Predominant pathological hallmarks of Alzheimer’s (AD) include the region-specific deposition of β amyloid (Aβ) plaques, vascular amyloidosis, and a number of distinct neurodegenerative changes. These involve the formation of dystrophic neurites and neuritic plaques, cytoskeletal alterations, and synaptic and neuronal loss. Astrocytosis and microgliosis are also evident in affected brain regions. Transgenic (tg) mice overexpressing a mutant form of the β-amyloid precursor protein (APP 717 V→ F) develop several of these pathologies in an age- and region-dependent manner similar to AD. Aβ plaques in the transgenic mouse share many of the tinctorial and immunohistochemical properties of AD plaques, including the relative distribution of AβX-40 and AβX-42 isoforms and the presence of other plaque-associated proteins. Initial findings using immunoassays specific to unique forms of APP and Aβ suggest that APP levels do not dramatically change with increasing age in the mouse brains, and that region-specific variations in APP metabolism, local factors or deficits in distinct populations of neurons account for the deposition of brain Aβ. The PDAPP mouse is a relevant and efficient model system to identify mechanistic properties of the disease process and offers novel opportunities to test potential therapeutics.
Databáze: OpenAIRE