Immunohistochemical study of semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 in the hippocampal vasculature: pathological synergy of Alzheimer's disease and diabetes mellitus.
Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) is involved in vascular endothelial damage as well as in the vascular degeneration underlying diabetes mellitus and Alzheimer's disease (AD). Recent evidence suggests that classic pathological features of AD are more pronounced in diabetic mellitus patients. To investigate the expression and distribution of SSAO/VAP-1 in the two pathologies, we have performed an immunohistochemical study in human hippocampal vessels of AD, AD with diabetic mellitus (ADD), diabetic mellitus (DM), and nondemented (ND) patients. The present results demonstrate major vessel accumulation of both SSAO/VAP-1 and amyloid-β immunolabeling intensity in ADD compared with AD patients. Interestingly, nearly damaged vessels with high levels of SSAO/VAP-1 also showed increased oxidative damage markers (AGE, RAGE, and SOD-1) and glial activation (GFAP and HLA). Overall, this work suggests that high vascular SSAO/VAP-1 levels in human hippocampus may contribute to vascular degeneration, which can explain the severe progression in patients with both pathologies.
Departament de Bioquímica i Biologia Molecular, Institut de Neurociències, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. tonyvalente@gmail.com
Tony
T
Valente
Alejandro
A
Gella
Montse
M
Solé
Núria
N
Durany
Mercedes
M
Unzeta
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D006631:Amine Oxidase (Copper-Containing) / Q000032:analysis / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000502:physiology; D048909:Diabetes Complications / Q000378:metabolism / Q000473:pathology; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006680:HLA Antigens / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D058225:Plaque, Amyloid / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D005904:Glial Fibrillary Acidic Protein; D017127:Glycation End Products, Advanced; D006680:HLA Antigens; C000606290:SOD1 protein, human; D019010:Vascular Cell Adhesion Molecule-1; D016875:tau Proteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D006631:Amine Oxidase (Copper-Containing)