Morphological and biochemical changes in the aging brain: pathophysiological and possible therapeutic consequences.

Significant reduction in brain weight and in the number of cortical neurons with increase of astroglia in aging brain and SDAT are associated with decreased synthesis and turnover of some neurotransmitters, particularly affecting the DAergic system. Progressive loss of TH activity reaching in SDAT almost the low levels of Parkinson disease is associated with progressive decline in DA concentration in the nigro-striatal system. Increase in MAO-B activity and in the ratio of MAO-B: MAO-A reported by some authors in aging brain and SDAT, however, was not confirmed in human frontal cortex in both Parkinson disease and SDAT. However, the location of both types of MAO in human brain is debatable, since preliminary studies indicate that, unlike in rat brain, MAO-B appears to be the major degradating enzyme of biogenic amines in human brain, while MAO-A might be associated, at least in part, with neuronal structures. Reduction in DAergic parameters in aging brain are also reflected in a decrease of adenylate cyclase activity and of D2 DA receptors. Animal data on decrease of DA-receptor density in the striatum with age were confirmed in human Parkinson disease and Alzheimer disease. These disturbances in neuronal feedback systems may be responsible for pathophysiological and behavioral changes in old age.