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

Despite a decade long universal publication in favor of the view on amyloid-beta (Abeta) as Alzheimer's disease culprit (solely neurotoxic for neurons and brain tissue), current scientific evidence leaves little doubt that Abeta serves an essential role at synapse and in synaptic structure-functional plasticity that underlie learning and memory. Therefore, the change of Abeta 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 Abeta(1-40) rescued long term potentiation (LTP, a major model for activity-dependent CNS plasticity), while cholesterol synthesis inhibition abolished the restorative action of the Abeta peptide. This study confirms that Abeta 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-beta protein precursor (AbetaPP) are a true model for Alzheimer's type neurodegeneration.