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Authors: Pomara, Nunzio | Bruno, Davide

Article Type: Article Commentary

Abstract: In spite of compelling evidence linking amyloid-β (Aβ) disturbances to the pathophysiology of Alzheimer’s disease (AD), Aβ-based treatments have consistently failed to produce any beneficial effects both in mild cognitive impairment (MCI) and AD, even with successful reductions of toxic aggregated and soluble Aβ species. Before abandoning both the hypothesis and approach, there is a need to examine some overlooked factors that may have contributed to the lack of efficacy, such as the potential drug-induced increases in neuronal hyperactivity leading to adverse cognitive effects. In particular, we posit that selective cholinergic and noradrenergic pathways will be especially vulnerable to this …adverse effect. If confirmed, this idea could help identify a potentially preventable and treatable obstacle for enhancing the efficacy of therapeutic agents in MCI and AD. Show more

Keywords: Alzheimer’s disease, amyloid-β-based treatments, cognitive dysfunction, mild cognitive impairment, neuronal hyperactivity

DOI: 10.3233/ADR-180077

Citation: Journal of Alzheimer's Disease Reports, vol. 2, no. 1, pp. 165-167, 2018