Inflammation and Alzheimer disease.
Inflammatory mechanisms are active in patients with Alzheimer disease. Serum elevations of acute phase proteins such as alpha 1-antichymotrypsin, along with deposition of inflammatory cytokines in the brain, suggest a "cerebral acute phase response" contributing to amyloid deposition and tissue destruction. Activated microglia possessing HLA-DR surface markers accumulate around amyloid plaques. The complement cascade leads to generation of the membrane attack complex, which may directly damage neuronal membranes. This growing body of evidence suggests that empirical trials of anti-inflammatory drugs are now appropriate to test the hypothesis that suppression of these mechanisms will slow the rate of progression of Alzheimer disease. Several drugs useful in the treatment of rheumatic diseases are candidates for study in Alzheimer disease, including glucocorticoids, antimalarial drugs, and colchicine. Pilot studies of the synthetic glucocorticoid prednisone indicate that treatment with a moderate dose is well tolerated in patients with Alzheimer disease, and suppresses serum levels of acute phase proteins. Based on this experience, a multicenter parallel-design placebo-controlled trial has been initiated with Alzheimer's Disease Cooperative Study to determine whether treatment with prednisone can slow the rate of progression of Alzheimer disease.
Aisen
P S
PS
Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001921:Brain / Q000276:immunology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005938:Glucocorticoids / Q000627:therapeutic use; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D009474:Neurons / Q000473:pathology; D010865:Pilot Projects; D011241:Prednisone / Q000627:therapeutic use
D000209:Acute-Phase Proteins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D005938:Glucocorticoids; D006684:HLA-DR Antigens; D011241:Prednisone