Pathophysiology of the Alzheimer's syndrome

A formulation of the pathophysiology of dementia of the Alzheimer's type, particularly that of later onset, proposes that it is a convergence syndrome in which a variety of genetic and environmental abnormalities can contribute to characteristic brain damage. This is consistent with currently available epidemiologic and risk factor data, molecular neuropathologic findings, and data on the brain-behavior relationship in the syndrome. This model can accommodate the typical findings in dementia of the Alzheimer's type, including mitochondrial damage, selective loss of neurons and synapses, cytoskeletal abnormalities, localized inflammatory reaction, and amyloidosis, implicating loss of synapses as the proximal cause of clinical dementia and emphasizing the mechanistic role of mitochondrial damage in nerve cell damage and metabolic dysfunction. This model implies that different therapies may be directed at different contributing causes of dementia of the Alzheimer's type in the individual patient and that subgroups of patients can be expected to respond differently to different treatments.