The essential role of inflammation and induced gene expression in the pathogenic pathway of Alzheimer's disease.
Alzheimer's disease is among the most common diseases of advanced age affecting almost one out of ten individuals who survive beyond the age of 65 years, and an another 10% for each additional decade of the life-span. The prognosis of the disease is an inexorable decline of mental functions leading to complete dependence on caretakers in the late stages of the disease. Alzheimer's disease will become a steadily increasing financial health-care problem in the industrialized world with the increasing longevity and ageing of the population. To-date there are no effective therapeutics. However, during the last years promising findings suggest that anti-inflammatory treatment strategies might be efficient. Here, we will review the experimental and epidemiological findings which support the idea that inflammatory mechanisms play an important role in Alzheimer's disease pathogenesis. The review of the experimental findings will be focussed on the amyloid-associated proteins, alpha1-antichymotrypsin and apolipoprotein E, as well as the major cytokines. In addition, the epidemiological studies on non-steroidal anti-inflammatory drugs and traumatic head injury will be summarized. We hypothesize a pathogenic model for Alzheimer's disease in which the expression of amyloid-associated proteins/pathological chaperones, induced by inflammatory cytokines, plays an essential role in accelerating the disease progress, and suggest potential targets for drug discovery based on such a model.
Nilsson
L
L
Department of Neurobiology, Harvard Medical School and Division of Hematology, Boston, MA 02115, USA.
Rogers
J
J
Potter
H
H
D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D000682:Amyloid / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000502:physiology*; D004660:Encephalitis / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans
D000682:Amyloid; D016207:Cytokines