title: Neuronal hyperactivity--A key defect in Alzheimer's disease?
abstract: Traditionally, the impairment of cognitive functions in Alzheimer's disease (AD) is thought to result from a reduction in neuronal and synaptic activities, and ultimately cell death. Here, we review recent in vivo evidence from mouse models and human patients indicating that, particularly in early stages of AD, neuronal circuits are hyperactive instead of hypoactive. Functional analyses at many levels, from single neurons to neuronal populations to large-scale networks, with a variety of electrophysiological and imaging techniques have revealed two forms of AD-related hyperactivity and provided first insights into the synaptic mechanisms. The unexpected finding that hyperactivity is an early neuronal dysfunction represents a major conceptual shift in our understanding of AD that may have important implications for the development of therapeutic approaches.
authors.affiliation: Institute of Neuroscience, Technische Universität München, München, Germany.|Department of Psychiatry and Psychotherapy, Technische Universität München, München, Germany.|Munich Cluster for Systems Neurology (SyNergy) and Center for Integrated Protein Sciences (CIPSM), Technische Universität München, Munich, Germany.
authors.forename: Marc Aurel
authors.initials: MA
authors.lastname: Busche
authors.affiliation: Institute of Neuroscience, Technische Universität München, München, Germany.|Munich Cluster for Systems Neurology (SyNergy) and Center for Integrated Protein Sciences (CIPSM), Technische Universität München, Munich, Germany.
authors.forename: Arthur
authors.initials: A
authors.lastname: Konnerth
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D025461:Feedback, Physiological; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D009474:Neurons / Q000502:physiology*; D058225:Plaque, Amyloid / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission
keywords: Alzheimer's disease; amyloid-ß; biomedicine; brain imaging; mouse models; neuronal dysfunction; neuronal hyperactivity