Age-Related Changes in the Synaptic Density of Amyloid-beta Protein Precursor and Secretases in the Human Cerebral Cortex

Amyloid-beta protein precursor (A beta PP) is involved in synaptic formation and function. In the human cingulate cortex, A beta PP was preferentially located in the presynaptic active zone as in rodents, indicating a preserved subsynaptic A beta PP distribution across species and brain regions. Synaptic A beta PP immunoreactivity was decreased with aging in cortical samples collected from autopsies of males (20-80 years), whereas the synaptic levels of alpha-secretase (ADAM10) and beta-secretase (BACE1) did not significantly change. Decreased A beta PP levels may be related to lower allostasis of synapses in the aged brain and their greater susceptibility to dysfunction characteristic of the onset of neurodegenerative disorders.