Astrocytic calcium/zinc binding protein S100A6 over expression in Alzheimer's disease and in PS1/APP transgenic mice models.
Astrocytes recruitment and activation are a hallmark of many neurodegenerative diseases including Alzheimer's disease (AD). We have previously observed an overexpression for S100A6 protein, a Ca(2+)/Zn(2+) binding protein presenting more affinity for zinc than for calcium, in amyotrophic lateral sclerosis (ALS). Here we demonstrated in AD patients but also in two different AD mouse models, that astrocytic S100A6 protein was homogeneously up-regulated within the white matter. However, within the grey matter, almost all S100A6 immunoreactivity was concentrated in astrocytes surrounding the Abeta amyloid deposits of senile plaques. These S100A6 neocortex labelled astrocytes were also positive for the glial fibrillary acidic protein (GFAP) and S100B protein. Contrasting with S100A6, the distribution for S100B and GFA astrocytic labelled cells was not restricted to the Abeta amyloid deposit in grey matter, but widely distributed throughout the neocortex. Coupling the knowledge that biometals such as zinc are highly concentrated in the amyloid deposits in AD and S100A6 having a high affinity for Zn(2+) may suggest that S100A6 plays a role in AD neuropathology.
Boom
Alain
A
Laboratory of Histology, Neuroanatomy and Neuropathology, School of Medicine, Université Libre de Bruxelles, 808, route de Lennik, Bldg GE, 1070 Brussels, Belgium.
Pochet
Roland
R
Authelet
Michele
M
Pradier
Laurent
L
Borghgraef
Peter
P
Van Leuven
Fred
F
Heizmann
Claus W
CW
Brion
Jean-Pierre
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D053764:Presenilin-1
D016564:Amyloid beta-Protein Precursor; C111922:Cacybp protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1