Activation of the contact system in cerebrospinal fluid of patients with Alzheimer disease.
Several converging lines of evidence suggest that beta-amyloid and inflammation may be linked in the pathogenesis of Alzheimer disease (AD), but the mechanism of beta-amyloid neurotoxicity is unclear. In this study, by demonstrating that high molecular weight kininogen may be massively cleaved in the cerebrospinal fluid (CSF) of patients with AD, we provide evidence of the potential involvement of the contact system in the inflammatory processes taking place in this disease. In the CSF of patients with neuroimmune inflammatory disease (multiple sclerosis, chronic inflammatory demyelinating polyneuropathy), there was no evidence of increased cleavage of high molecular weight kininogen, suggesting that this finding may be characteristic of the Alzheimer brain. The data obtained from in vitro experiments seem to indicate that the cleavage of high molecular weight kininogen in vivo may be the result of the interaction of beta-amyloid with factor XII and of kallikrein generation. The actual relevance of such a phenomenon remains to be established in vivo. However, the demonstration that the contact system may be activated in the brains of Alzheimer patients points to the potential involvement of the kallikrein-kinin system in the inflammatory process of this disease.
Bergamaschini
L
L
Institute of Internal Medicine, University of Milan, Italy.
Parnetti
L
L
Pareyson
D
D
Canziani
S
S
Cugno
M
M
Agostoni
A
A
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology; D015153:Blotting, Western; D003711:Demyelinating Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000503:physiopathology; D005174:Factor XII / Q000502:physiology; D005260:Female; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology*; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000502:physiology; D007704:Kininogens / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D015213:Neuroimmunomodulation / Q000502:physiology
D016229:Amyloid beta-Peptides; D007704:Kininogens; D005174:Factor XII; D007610:Kallikreins