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

Bearer, Elaine L. and Manifold-Wheeler, Brett C. and Medina, Christopher S. and Gonzales, Aaron and Cháves, Frances and Jacobs, Russell E. (2018) Alterations of functional circuitry in aging brain and the impact of mutated APP expression. Neurobiology of Aging, 70 . pp. 276-290. ISSN 0197-4580. doi:10.1016/j.neurobiolaging.2018.06.018.

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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 hypothesis 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.

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Jacobs, Russell E.0000-0002-1382-8486
Additional Information:© 2018 Published by Elsevier. Received 31 March 2017, Revised 17 June 2018, Accepted 18 June 2018, Available online 28 June 2018.
Subject 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
Record Number:CaltechAUTHORS:20180628-144201687
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Official Citation:Elaine L. Bearer, Brett C. Manifold-Wheeler, Christopher S. Medina, Aaron G. Gonzales, Frances L. Chaves, Russell E. Jacobs, Alterations of functional circuitry in aging brain and the impact of mutated APP expression, Neurobiology of Aging, Volume 70, 2018, Pages 276-290, ISSN 0197-4580, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:87445
Deposited By: George Porter
Deposited On:29 Jun 2018 15:14
Last Modified:15 Nov 2021 20:48

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