Increased mtDNA mutations with aging promotes amyloid accumulation and brain atrophy in the APP/Ld transgenic mouse model of Alzheimer's disease.

ABSTRACT:

Background

The role of mitochondrial dysfunction has long been implicated in age-related brain pathology, including Alzheimer's disease (AD). However, the mechanism by which mitochondrial dysfunction may cause neurodegeneration in AD is unclear. To model mitochondrial dysfunction in vivo, we utilized mice that harbor a knockin mutation that inactivates the proofreading function of mitochondrial DNA polymerase γ (PolgA D257A), so that these mice accumulate mitochondrial DNA mutations with age. PolgA D257A mice develop a myriad of mitochondrial bioenergetic defects and physical phenotypes that mimic premature ageing, with subsequent death around one year of age.

Results

We crossed the D257A mice with a well-established transgenic AD mouse model (APP/Ld) that develops amyloid p

SUBMITTER: Kukreja L 

PROVIDER: S-EPMC4028006 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature