title: Neuronal activity and amyloid plaque pathology: an update.
abstract: A breakthrough in Alzheimer's disease (AD) research came with the discovery of the link between activity-dependent release of amyloid-β (Aβ) from neurons and formation of amyloid plaques. Along with elucidating the cellular basis of behavioral-dependent fluctuations in Aβ levels in the brain, insights have been gained toward understanding the mechanisms that warrant selective vulnerability of various forebrain circuits to amyloid pathology. The notion of elevated activity as a source of excessive Aβ production and plaque formation is, however, in conflict with ample electrophysiological data, which demonstrate exceedingly intense activity (both intrinsic and synaptic) of neurons in several brain regions that are spared or marginally affected by amyloid plaques of AD. Thus, the link between the functional load of brain circuits and their vulnerability to amyloidosis, while evident, is also complex and remains poorly understood. Here, we discuss emerging data suggestive of a major role for super-intense synchronous activity of cortical and limbic networks in excessive Aβ production and plaque formation. It is proposed that dense recurrent wiring of associative areas prone to epileptic seizures might be of critical relevance to their higher susceptibility to plaque pathology and related functional impairments.
authors.affiliation: International Centre for Neurotherapeutics, Dublin City University, Dublin, Republic of Ireland.
authors.forename: Saak V
authors.initials: SV
authors.lastname: Ovsepian
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum Munich, Neuherberg, Germany.
authors.forename: Valerie B
authors.initials: VB
authors.lastname: O'Leary
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology*; D058225:Plaque, Amyloid / Q000473:pathology*; D016548:Prosencephalon / Q000503:physiopathology*; D012640:Seizures / Q000209:etiology
chemical_list: D016229:Amyloid beta-Peptides; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; amyloid-β peptide; hetero-modal associative cortex; neuronal synchrony; non-convulsive seizure