Disrupted mitochondrial response to nutrients is a presymptomatic event in the cortex of the APP^SAA knock-in mouse model of Alzheimer's disease.

ABSTRACT:

Introduction

Reduced brain energy metabolism, mammalian target of rapamycin (mTOR) dysregulation, and extracellular amyloid beta (Aβ) oligomer (xcAβO) buildup are some well-known Alzheimer's disease (AD) features; how they promote neurodegeneration is poorly understood. We previously reported that xcAβOs inhibit nutrient-induced mitochondrial activity (NiMA) in cultured neurons. We now report NiMA disruption in vivo.

Methods

Brain energy metabolism and oxygen consumption were recorded in heterozygous amyloid precursor protein knock-in (APP^SAA) mice using two-photon fluorescence lifetime imaging and multiparametric photoacoustic microscopy.

Results

NiMA is inhibited in APP^SAA mice before other defects are detected in these Aβ-producing animals tha

SUBMITTER: Norambuena A 

PROVIDER: S-EPMC11485302 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature