Quantitative assessment of possible age-related change in synaptic numbers in the human frontal cortex.

To investigate possible age-associated changes in human synaptic connectivity, superior-middle frontal cortex (Brodmann area 9) was evaluated with ultrastructural techniques. Short post mortem autopsy tissue was obtained from 37 cognitive normal individuals ranging in age from 20 to 89 years. A minimum of five subjects represented each decade of life. Synaptic volume density (Nv) was quantified in lamina III and V of the superior-middle frontal cortex employing the physical disector. The stereological assessment demonstrated maintenance of Nv in both lamina III and V of the frontal cortex. The lack of synaptic decline in the frontal cortex in neurologically normal individuals older than 65 years lends support to the idea that many stereotypic views of age-related changes in the CNS do not apply to all brain regions. It also suggests that synaptic loss observed in pathological conditions such as Alzheimer's disease, may be the result of the disease process and not a consequence of normal aging.