Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells.

Evidence suggests that amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer's disease (AD) and it has been recently proposed that mitochondria are involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Here we investigated the specific effects of Abeta on mitochondrial function under physiological conditions. Mitochondrial respiratory functions and energy metabolism were analyzed in control and in human wild-type amyloid precursor protein (APP) stably transfected human neuroblastoma cells (SH-SY5Y).

Mitochondrial dysfunction induced by disease relevant AbetaPP and tau protein mutations.

Alzheimer's disease is characterized by two major pathological hallmarks: extracellular plaques consisting of amyloid beta peptide and neurofibrillary tangles composed of hyperphosphorylated tau protein. Mutations in the amyloid beta-protein precursor (AbetaPP) have been linked to familial Alzheimer's disease. They are leading to increased amyloid beta production.

Apolipoprotein E epsilon 4 is associated with an increased vulnerability to cell death in Alzheimer's disease.

The presumption to suffer from Alzheimer's disease (AD) accelerates with aging. One important risk factor seems to be the isoform epsilon 4 of the apolipoprotein E gene (Apo epsilon 4), which increases the risk to develop AD at an earlier age. Furthermore, convincing evidence is provided that apoptotic cell death mechanisms play an important role in neuronal cell death in AD.

Mitochondrial dysfunction in sporadic and genetic Alzheimer's disease.

Increasing evidence suggests an important role of mitochondrial dysfunction in the pathogenesis of many common age-related neurodegenerative diseases, including Alzheimer's disease (AD). AD is the most common neurodegenerative disorder characterized by dementia, memory loss, neuronal apoptosis and eventually death of the affected individuals. AD is characterized by two pathologic hallmark lesions that consist of extracellular plaques of amyloid-beta peptides and intracellular neurofibrillary tangles composed of hyperphosphorylated microtubular protein tau.

Elevated nitric oxide production mediates beta-amyloid-induced mitochondria failure.

Mitochondrial dysfunction has been identified in a large proportion of neurodegenerative disorders including Alzheimer's disease (AD). In addition, the involvement of nitric oxide (NO) has been implicated in the pathogenesis of AD. Thus, we investigated the effects of the Swedish double mutation (K670M/N671L) in the beta-amyloid precursor protein (APPsw) on NO levels and mitochondrial function in PC12 cells.