Aβ Toxicity in Alzheimer's Disease

Alzheimer's Disease (AD), the most common age-related neurodegenerative disorder, is characterized by progressive cognitive decline, synaptic loss, the formation of extracellular beta-amyloid plaques and intracellular neurofibrillary tangles, and neuronal cell death. Despite the massive neuronal loss in the 'late stage' of disease, dendritic spine loss represents the best pathological correlate to the cognitive impairment in AD patients. The 'amyloid hypothesis' of AD recognizes the A beta peptide as the principal player in the pathological process. Many lines of evidence point out to the neurotoxicity of A beta, highlighting the correlation between soluble A beta oligomer accumulation, rather than insoluble A beta fibrils and disease progression. Pathological increase of A beta in AD brains, resulting from an imbalance between its production, aggregation and clearance, might target mitochondrial function promoting a progressive synaptic impairment. The knowledge of the exact mechanisms by which A beta peptide impairs neuronal function will help us to design new pharmacological tools for preventing AD neurodegeneration.