Alzheimer Disease

Significant progress has been made since the 1980s in understanding the neurobiology of Alzheimer disease (AD). The clinical syndrome of AD results from synaptic dysfunction and death of neurons in specific brain regions and circuits, particularly populations of nerve cells subserving memory and cognition. The pathological hallmarks are the extracellular deposition of -pleated assemblies of A-peptide (amyloid plaques) and intracellular aggregates of hyperphosphorylated tau protein (neurofibrillary tangles). Utilization of transgenic models of AD has advanced understanding of the pathogenesis of this disease and resulted in the discovery of therapeutic targets. The first attempts to implement novel antiamyloid treatments in mild to moderate AD had disappointing results, suggesting that therapy should be given much earlier in the course of the disease. Recognition that pathophysiological processes of AD begin decades before clinical symptoms appear calls for the development of tools for early diagnosis (imaging and biomarkers) and early treatment.