Biochemical substrates in normal aging and Alzheimer's disease.

In individuals above 60 years of age, an age-related decrease in the concentrations of dopamine, noradrenaline, and 5-hydroxytryptamine has been found. This may indicate a neuron loss. As the metabolites are not simultaneously reduced, a compensatory mechanism would seem to exist. In the hypothalamus there are significant positive correlations between the neuropeptides galanin and corticotropin-releasing factor on the one hand, and age over 60 on the other. In brains from patients with dementia of Alzheimer type there are reduced concentrations of cholineacetyl transferase. However, in some brain areas reduced concentrations of 5-hydroxytryptamine, dopamine, and noradrenaline have also been found. The metabolites homovanillic acid and 5-hydroxyindolacetic acid are also reduced. These findings indicate that there is not only a neuron loss in these brains but also a dysfunction of the remaining neurons, reducing the compensatory capacity of the brain. Postmortem investigations of hypothalamus from Alzheimer brains have shown reduced concentrations of 5-hydroxytryptamine. However, the concentrations of galanin, arginin, vasopressin, and somatostatin were significantly increased. The latter may be the result of a disturbed higher control over the hypothalamus. Hypothalamic dysfunction is of interest with regard to the neuroendocrine disturbances seen in Alzheimer-demented patients. Investigations of patients with vascular dementia have suggested the same type of neurotransmitter disturbances as in Alzheimer's disease.