The neurochemistry of Alzheimer's disease

This paper gives a review of the neurochemical alterations that characterize Alzheimer's disease. The quantitative distribution of each compound or group of compounds over the central nervous system and their concentrations in the cerebrospinal fluid as well as receptor interactions and densities are discussed. Where possible, these neurochemical alterations are correlated with cognitive and noncognitive symptoms. A degeneration of the cholinergic nucleus basalis of Meynert characterizes Alzheimer's disease and results in neocortical cholinergic deficits correlating with cognitive impairment. Catecholaminergic changes include prominent cell loss of the noradrenergic locus coeruleus leading to decreased norepinephrine concentrations in cerebrospinal fluid and several cortical and subcortical areas. Modest, but identical trends are reported for epinephrine and dopamine. The former alterations are correlated with depression and psychosis in Alzheimer's disease. The serotonergic nucleus raphe dorsalis shows evidence of degeneration, causing a decreased serotonin content of the neocortex and the cerebrospinal fluid which is correlated with both cognitive and noncognitive symptomatology. Several - often less understood - changes of amino acids and neuropeptides will be reviewed. Finally, the neurochemical aspects of cytokine-mediated inflammatory reactions and of oxidative stress in the physiopathology of Alzheimer's disease are reviewed.