Excessive/Aberrant and Maladaptive Synaptic Plasticity: A Hypothesis for the Pathogenesis of Alzheimer’s Disease

The amyloid hypothesis for the pathogenesis of Alzheimer’s disease (AD) is widely accepted. Last year, the US Food and Drug Administration considered amyloid-β peptide (Aβ) as a surrogate biomarker and approved an anti-Aβ antibody, aducanumab, although its effectiveness in slowing the progression of AD is still uncertain. This approval has caused a great deal of controversy. Opinions are divided about whether there is enough evidence to definitely consider Aβ as a causative substance of AD. To develop this discussion constructively and to discover the most suitable therapeutic interventions in the end, an alternative persuasive hypothesis needs to emerge to better explain the facts. In this paper, I propose a hypothesis that excessive/aberrant and maladaptive synaptic plasticity is the pathophysiological basis for AD.