Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease

• DOI: 10.1093/hmg/ddr381
• Publication Date: 2011-08-27T00:18:34Z
• Authors: M. J. Calkins; M. Manczak; P. Mao; U. Shirendeb; P. H. Reddy
• Keywords: Axoplasmic transport

Increasing evidence suggests that the accumulation of amyloid beta (Aβ) in synapses and synaptic mitochondria causes mitochondrial failure degeneration Alzheimer's disease (AD). The purpose this study was to better understand effects Aβ activity alterations neurons from a mouse model AD. Using primary well-characterized precursor protein transgenic (AβPP) (Tg2576 line), for first time, we studied activity, including axonal transport mitochondria, dynamics, morphology function. Further, also nature Aβ-induced alterations, cell death Tg2576 mice, sought determine whether mitochondria-targeted antioxidant SS31 could mitigate oligomeric Aβ. We found significantly decreased anterograde movement, increased fission fusion, abnormal proteins defective function AβPP mice compared with wild-type (WT) neurons. Transmission electron microscopy revealed large number small structurally damaged broken cristae an apoptotic neuronal relative WT Our results intraneuronal Aβ, leading deficiencies, ultimately causing neurodegeneration cultures. However, restored viability, percentage indicating protects toxicity.