Convergence of Amyloid-β and Tau Pathologies on Mitochondria In VivoReportar como inadecuado

Convergence of Amyloid-β and Tau Pathologies on Mitochondria In Vivo - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Molecular Neurobiology

, Volume 41, Issue 2–3, pp 107–114

First Online: 09 March 2010Received: 06 November 2009Accepted: 12 February 2010


The histopathological characteristics of Alzheimer’s disease AD are amyloid-β Aβ containing plaques and neurofibrillary tangles NFTs as well as neuronal and synaptic loss. Until today, the underlying mechanisms of the interplay of plaques and tangles remained unresolved. There is increasing evidence that mitochondrial dysfunction might be a possible link, as revealed by studies in several APP and tau transgenic mouse models. Recently, we examined mitochondrial function in a novel triple transgenic mouse model pR5-APP-PS2—AD mice—that combines both pathologic features of the disease in brain. Using comparative, quantitative proteomics iTRAQ and mass spectroscopy, we found a massive deregulation of 24 proteins, of which one third were mitochondrial proteins mainly related to complexes I and IV of the oxidative phosphorylation system OXPHOS. Remarkably, deregulation of complex I was related to tau, whereas deregulation of complex IV was Aβ dependent, both at the protein and activity levels. The AD mice showed synergistic effects of Aβ and tau already at the age of 8 months, resulting in a depolarized mitochondrial membrane potential. At 12 months, the strongest defects on OXPHOS, synthesis of ATP and reactive oxygen species, were exhibited in the AD mice, again emphasizing synergistic, age-associated effects of Aβ and tau in impairing mitochondria. This review highlights the convergence of Aβ and tau on mitochondria and establishes a molecular link in AD pathology in vivo.

KeywordsAlzheimer-s disease Amyloid-β peptide Energy metabolism Mitochondria Oxidative phosphorylation system OXPHOS Tau protein Transgenic AD mouse models  Download fulltext PDF

Autor: Anne Eckert - Kathrin L. Schulz - Virginie Rhein - Jürgen Götz


Documentos relacionados