Abstract
Mutations in Amyloid Precursor Protein (APP) and Presenilin 1 and 2 (PS1, PS2) proteins underlie the progression of familial Alzheimer’s Disease (AD). Neurofibrillary tangles and amyloid plaques are the hallmark of AD. The disease mechanism remains elusive, however, mounting data indicate implication of mitochondrial dysfunction and energetic stress early in disease progression. We have previously demonstrated that loss of mitochondrial motility observed in embryonic neurons from APP/PS1 and PS1 transgenic mice was among the earliest abnormalities detected in these animals prior to the loss of mitochondrial function, the onset of memory or neurological phenotype or deposition of amyloid plaques. These structures were most likely associated with altered mitochondrial fission or fusion. This study is designed to reveal the details of morphological changes of mitochondria using 3D reconstruction of serial sections obtained with transmission electron microscopy (TEM). We aimed to quantify the specific changes in mitochondrial shape, length, width, formation of abnormal structures, distribution, and cristae organization in young (20 weeks) and old (52-54 weeks) NTG and APP/PS1 throughout the CA1 & CA3 regions of the hippocampus. Defining the mechanism underlying changes in mitochondria morphology in FAD mice could help to understand the disease mechanism and suggest therapeutic interventions.
Faculty Sponsors
Dr. James Munoz
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-12-2013 1:00 PM
End Date
4-12-2013 5:30 PM
A Novel Method of 3D Reconstruction of Mitochondrial Morphology in Mouse Models of Alzheimer's Disease
Alvin Sherman Library
Mutations in Amyloid Precursor Protein (APP) and Presenilin 1 and 2 (PS1, PS2) proteins underlie the progression of familial Alzheimer’s Disease (AD). Neurofibrillary tangles and amyloid plaques are the hallmark of AD. The disease mechanism remains elusive, however, mounting data indicate implication of mitochondrial dysfunction and energetic stress early in disease progression. We have previously demonstrated that loss of mitochondrial motility observed in embryonic neurons from APP/PS1 and PS1 transgenic mice was among the earliest abnormalities detected in these animals prior to the loss of mitochondrial function, the onset of memory or neurological phenotype or deposition of amyloid plaques. These structures were most likely associated with altered mitochondrial fission or fusion. This study is designed to reveal the details of morphological changes of mitochondria using 3D reconstruction of serial sections obtained with transmission electron microscopy (TEM). We aimed to quantify the specific changes in mitochondrial shape, length, width, formation of abnormal structures, distribution, and cristae organization in young (20 weeks) and old (52-54 weeks) NTG and APP/PS1 throughout the CA1 & CA3 regions of the hippocampus. Defining the mechanism underlying changes in mitochondria morphology in FAD mice could help to understand the disease mechanism and suggest therapeutic interventions.
