Comparative Localization of ADAMs 10 and 15 in Human Cerebral Cortex Normal Aging, Alzheimer Disease and Down Syndrome

Using immunohistochemical techniques we studied the light microscopic localization of ADAMs (A Disintegrin And Metalloprotease) 10 and 15 in different neocortical areas of the human brain during normal aging, and also in patients with Alzheimer disease (AD) and Down syndrome (DS). ADAM 10, a putative alpha-secretase involved in Notch signaling, was found in neurons of the perinatal cortex. During aging there is an increase in intraneuronal staining intensity and in the number of cortical nerve cells that contain the enzyme. Furthermore, in AD and DS brains ADAM 10 immunoreactivity was associated with diffuse and neuritic plaques. ADAM 15 was detected in perinatal cortical pyramidal cells; during aging there was also an increase in intracellular staining and the number of stained cells per volume (cell density). In AD brains ADAM 15 was seen in a few diffuse plaques. Morphometric analysis revealed a significant reduction of ADAM 10 but not ADAM 15 immunoreactive neurons in AD brains in comparison to controls. Our findings support the idea that ADAM 10 is involved in the pathophysiology of AD and DS. ADAM 15 might be linked to AD via interaction with integrin and/or src protein tyrosine kinases.