Discrete pools of oligomeric amyloid- β track with spatial learning deficits in a mouse model of Alzheimer amyloidosis.

Discrete pools of oligomeric amyloid-β track with spatial learning deficits in a mouse model of Alzheimer amyloidosis. Am J Pathol. 2017 Dec 14;: Authors: Chiang ACA, Fowler SW, Reddy R, Pletnikova O, Troncoso JC, Sherman MA, Lesne SE, Jankowsky JL Abstract Despite increasing appreciation that oligomeric amyeloid beta (Aβ) may contribute to cognitive decline of Alzheimer disease, defining the most critical forms has been thwarted by the changeable nature of these aggregates and the varying methods used for detection. Here, using a broad approach, we quantified Aβ oligomers during the evolution of cognitive deficits in an aggressive model of Aβ amyloidosis. Amyloid precursor protein/tetracycline transactivator mice underwent behavioral testing at 3, 6, 9, and 12 months of age to evaluate spatial learning and memory, followed by histological assessment of amyloid burden and biochemical characterization of oligomeric Aβ species. Transgenic mice displayed progressive impairments in acquisition and immediate recall of the trained platform location. Biochemical analysis of cortical extracts from behaviorally tested mice revealed distinct age-dependent patterns of accumulation in mulitple oligomeric species. Dot blot analysis demonstrated that non-fibrillar Aβ oligomers (A11) were highly soluble and extracted into a fraction enriched for extracellular proteins, whereas pre-fibrillar (OC) species required high-detegerent conditions to ...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research