Overexpression of semicarbazide sensitive amine oxidase in the cerebral blood vessels in patients with Alzheimer's disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Semicarbazide sensitive amine oxidase (SSAO) metabolizes oxidative deamination of primary aromatic and aliphatic amines, and, in the brain, it is selectively expressed in blood vessels. SSAO expression is examined, by immunohistochemistry with a purified polyclonal antibody to SSAO from bovine lung, in the brains of subjects with Alzheimer disease (AD; n=10), cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; n=2), and age-matched controls (n=8). SSAO immunoreactivity is restricted to meningeal and parenchymal blood vessels in control and diseased brains. Yet, a marked and selective increase in SSAO immunoreactivity occurs in association with betaA4 vascular amyloid deposits in patients with AD, and in the vicinity of the typical granular deposits in the blood vessels of gray and white matter in patients with CADASIL. Oxidative deamination of primary aromatic and aliphatic amines by SSAO produces ammonia, hydrogen peroxide and the corresponding aldehyde. Moreover, increased SSAO immunoreactivity is associated with increased Cu/Zn superoxide dismutase 1 expression restricted to abnormal blood vessels in diseased brains. Therefore, it is suggested that increased SSAO expression is a source of oxidative stress in the blood vessel wall in AD and CADASIL.
Ferrer
I
I
Institut de Neuropatologia, Hospital Princeps d'Espanya, L'Hospitalet de Llobregat (08907), Barcelona, Spain.
Lizcano
J M
JM
Hernández
M
M
Unzeta
Mercedes
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000503:physiopathology; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001808:Blood Vessels / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000201:enzymology* / Q000503:physiopathology; D015161:Dementia, Multi-Infarct / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018384:Oxidative Stress / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology*
D016229:Amyloid beta-Peptides; D006631:Amine Oxidase (Copper-Containing)