Alterations of functional circuitry in aging brain and the impact of mutated APP expression

Elaine L. Bearer, Brett C. Manifold-Wheeler, Christopher S. Medina, Aaron G. Gonzales, Frances L. Chaves, Russell E. Jacobs
2018 Neurobiology of Aging  
Alzheimer's disease (AD) is a disease of aging that results in cognitive impairment, dementia and death. Pathognomonic features of AD are amyloid plaques composed of proteolytic fragments of the amyloid precursor protein (APP) and neurofibrillary tangles composed of hyperphosphorylated tau protein. One type of familial Alzheimer's disease (FAD) occurs when mutant forms of APP are inherited. Both APP and tau are components of the microtubule-based axonal transport system, which prompts the
more » ... esis that axonal transport is disrupted in AD, and that such disruption impacts cognitive function. Transgenic mice expressing mutated forms of APP provide preclinical experimental systems to study AD. Here we perform manganese-enhanced magnetic resonance imaging (MEMRI) to study transport from hippocampus to forebrain in four cohorts of living mice: young and old wild-type and transgenic mice expressing a mutant APP with both Swedish and Indiana mutations (APPSwInd). We find that transport is decreased in normal aging and further altered in aged APPSwInd plaque-bearing mice. These findings support the hypothesis that transport deficits are a component of AD pathology and thus may contribute to cognitive deficits. Abstract Corresponding Author: Professor Keywords Amyloid precursor protein (APP); fast axonal transport; CA3 of the hippocampus; dentate gyrus; transgenic mice for Alzheimer's disease investigation; aging; Manganese-enhanced magnetic resonance imaging (MEMRI); cholinergic neurons; septal nuclei Bearer et al.
doi:10.1016/j.neurobiolaging.2018.06.018 pmid:30055413 pmcid:PMC6159914 fatcat:rkj5jkpwjne7zp3m5do5zcarca