title: Storm before the quiet: neuronal hyperactivity and Aβ in the presymptomatic stages of Alzheimer's disease.
abstract: Neuronal activity directly promotes the production and secretion of amyloid β (Aβ). Interestingly, neuronal hyperactivity can be observed in presymptomatic stages of both sporadic and familial Alzheimer's disease (AD) and in several AD mouse models. In this review, we will highlight the recent evidence for neuronal hyperactivity before or during the onset of cognitive defects in mild cognitive impairment. Furthermore, we review specific molecular mechanisms through which neuronal hyperactivity affects Aβ production and degradation. With these data, we will provide more insight into the 2-faced nature of neuronal hyperactivity: does enhanced neuronal activity during the presymptomatic stages of AD provide protection against the earliest disease processes or is it a pathogenic contributor to AD?
authors.affiliation: Department of Cell Biology and Histology, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Stargardt
authors.affiliation: Neuropsychiatric Disorders, Netherlands Institute for Neuroscience-An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, the Netherlands.
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
authors.affiliation: Neuroregeneration, Netherlands Institute for Neuroscience-An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, the Netherlands; Synaptic Plasticity and Behavior, Netherlands Institute for Neuroscience-An Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Amsterdam, the Netherlands. Electronic address: k.bossers@nin.knaw.nl.
authors.forename: Koen
authors.initials: K
authors.lastname: Bossers
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis* / Q000378:metabolism*; D000818:Animals; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D059748:Proteolysis
chemical_list: D016229:Amyloid beta-Peptides
keywords: Alzheimer's disease; Aβ; Disease progression; Neuronal hyperactivity; Synaptotoxicity