The role of synaptic proteins in Alzheimer's disease.

Synaptic damage is an early event common to neurodegenerative disorders such as Alzheimer's disease (AD) and is the best correlate to the cognitive impairment found in these patients. Recent studies have shown that several of the molecules involved in neurodegenerative disorders are in fact synaptic proteins with amyloidogenic potential (SPWAP). Here we propose a unified theory to explain the neurodegenerative process in AD based on the idea that abnormal folding and/or aggregation of these molecules leads to cell death. The most important predictions of this hypothesis are that: (1) there are other yet unknown SPWAP that might be involved in AD, and their identity can be predicted by defining what makes a protein amyloidogenic; (2) there are endogenous anti-amyloidogenic molecules that regulate the aggregation state of SPWAP; and (3) there might be forms of the disease associated with decreased production of endogenous anti-amyloidogenic molecules or with unbalance of pro- versus anti-amyloidogenic factors.