Affiliations: [a] International Centre for Neurotherapeutics, Dublin City University, Dublin, Republic of Ireland | [b] Institute of Radiation Biology, Helmholtz Zentrum Munich, Neuherberg, Germany
Correspondence:
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Correspondence to: Saak V. Ovsepian, International Centre for Neurotherapeutics, Dublin City University, Dublin, Republic of Ireland. Tel.: +49 1763 9885 983; Fax: +49 1763 9885 980; E-mail: saak.ovsepian@gmail.com
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.
