Soluble beta-amyloid leads to mitochondrial defects in amyloid precursor protein and tau transgenic mice

Eckert, Anne, Hauptmann, Susanne, Scherping, Isabel, Rhein, Virginie, Muller-Spahn, Franz, Gotz, Jürgen and Muller, Walter E. (2008) Soluble beta-amyloid leads to mitochondrial defects in amyloid precursor protein and tau transgenic mice. Neurodegenerative Diseases, 5 3-4: 157-159. doi:10.1159/000113689


Author Eckert, Anne
Hauptmann, Susanne
Scherping, Isabel
Rhein, Virginie
Muller-Spahn, Franz
Gotz, Jürgen
Muller, Walter E.
Title Soluble beta-amyloid leads to mitochondrial defects in amyloid precursor protein and tau transgenic mice
Journal name Neurodegenerative Diseases   Check publisher's open access policy
ISSN 1660-2854
1660-2862
Publication date 2008-03
Sub-type Article (original research)
DOI 10.1159/000113689
Open Access Status
Volume 5
Issue 3-4
Start page 157
End page 159
Total pages 3
Place of publication Basel, Switzerland
Publisher S Karger AG
Collection year 2014
Language eng
Formatted abstract
Background: Mitochondrial dysfunction has been identified in neurodegenerative disorders including Alzheimer's disease, where accumulation of β-amyloid (Aβ) and oxidative stress seem to play central roles in the pathogenesis, by probably directly leading to mitochondrial dysfunction.

Objective: In order to study the in vivo effect of Aβ load during aging, we evaluated the mitochondrial function of brain cells from transgenic mice bearing either mutant amyloid precursor protein (tgAPP) or mutant amyloid precursor protein and mutant PS1 (tgAPP/PS1) as well as from nontransgenic wild-type littermates. tgAPP mice exhibit onset of Aβ plaques at an age of 6 months, but the intracellular soluble Aβ load is already increased at 3 months of age. In contrast, onset of Aβ plaques starts at an age of 3 months in tgAPP/PS1 mice. In addition, we investigated the effects of different Aβ preparations on mitochondrial function of brain cells from tau transgenic mice.

Results: Of note, mitochondrial damage such as reduced mitochondrial membrane potential and ATP levels can already be detected in the brains from these mice before the onset of plaques. In agreement with our findings in tgAPP mice, soluble Aβ induced mitochondrial dysfunction in brain cells from tau transgenic mice.

Conclusion: Our results indicate that mitochondrial dysfunction is exacerbated by the presence of soluble Aβ species as a very early event during pathogenesis.  
Keyword β-Amyloid
β-Amyloid oligomers
Alzheimer's disease
Energy deficit
Mitochondrial dysfunction
P301L mutant tau
Transgenic mice
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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