Alzheimer's amyloid-beta (Aβ) is an essential synaptic protein, not neurotoxic junk

Abstract

Despite a decade long universal publication in favor of the view on amyloid-β (Aβ) as Alzheimer's disease culprit (solely neurotoxic for neurons and brain tissue), current scientific evidence leaves little doubt that Aβ serves an essential role at synapse and in synaptic structure-functional plasticity that underlie learning and memory. Therefore, the change of Aβ biology in Alzheimer's disease (as well as in a number of other human pathologies, including cardiovascular disease, neuromuscular junction disorders, NPC and Down's syndrome) may represent a physiological mechanism to compensate for impaired brain structure or function. In our own recent study Aβ1-40 rescued long term potentiation (LTP, a major model for activity-dependent CNS plasticity), while cholesterol synthesis inhibition abolished the restorative action of the Aβ peptide. This study confirms that Aβ protein is a functional player in synaptic structure-functional plasticity and in cholesterol neurochemical pathways. The article also calls for a need to critically re-evaluate a universal belief that transgenic mice with a transgene for amyloid-β protein precursor (AβPP) are a true model for Alzheimer's type neurodegeneration.