Affiliations: [a] Department of Pharmacology, Biocenter, University of Frankfurt, 60439 Frankfurt, Germany | [b] Neurobiology Research Laboratory, Psychiatric University Clinic, 4025 Basel, Switzerland | [x] Center for Neuroscience and Cell Biology, Institute of Physiology – Faculty of Medicine, University of Coimbra, 3004-504 Coimbra, Portugal | [y] Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal
Correspondence:
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Corresponding author: Prof. Dr. Walter E. Müller, Department of Pharmacology, Biocenter, N260, University of Frankfurt, Marie-Curie-Str. 9, 60439 Frankfurt, Germany. Tel.: +49 69 79829373; Fax: +49 69 79829374; E-mail: [email protected].
Abstract: Alzheimer's disease is characterized by two major pathological hallmarks: extracellular plaques consisting of amyloid β peptide and neurofibrillary tangles composed of hyperphosphorylated tau protein. Mutations in the amyloid β-protein precursor (AβPP) have been linked to familial Alzheimer's disease. They are leading to increased amyloid β production. Mutations in the tau gene have not been described in AD, but are leading to formation of neurofibrillary tangles very similar to filaments in AD brains, and are therefore of increasing relevance in AD research. Interestingly, our data indicate that mutations in AβPP gene and mutations in tau gene induce mitochondrial dysfunction and oxidative stress in cell culture models and transgenic mice. Thus, both Alzheimer relevant protein alterations seem to have synergistic actions probably at the level of mitochondria leading to synaptic dysfunction and apoptotic cell death.
