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.
Bernstein
Hans-Gert
HG
Hans-Gert.Bernstein@medizin.uni-magdeburg.de
Bukowska
Alicja
A
Krell
Dieter
D
Bogerts
Bernhard
B
Ansorge
Siegfried
S
Lendeckel
Uwe
U
D051722:ADAM Proteins; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000201:enzymology* / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; D002540:Cerebral Cortex / Q000201:enzymology* / Q000254:growth & development / Q000473:pathology; D002648:Child; D004314:Down Syndrome / Q000201:enzymology* / Q000503:physiopathology; D015536:Down-Regulation / Q000502:physiology; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D005333:Fetus; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D016023:Integrins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000201:enzymology; D017966:Pyramidal Cells / Q000201:enzymology; D015854:Up-Regulation / Q000502:physiology; D019061:src-Family Kinases / Q000378:metabolism
D016023:Integrins; D008565:Membrane Proteins; D019061:src-Family Kinases; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D051722:ADAM Proteins; C098660:ADAM15 protein, human; D008666:Metalloendopeptidases