Interleukin-1 in the genesis and progression of and risk for development of neuronal degeneration in Alzheimer's disease.
Interleukin-1 (IL-1), a key molecule in systemic immune responses in health and disease, has analogous roles in the brain where it may contribute to neuronal degeneration. Numerous findings suggest that this is the case. For example, IL-1 overexpression in the brain of Alzheimer patients relates directly to the development and progression of the cardinal neuropathological changes of Alzheimer's disease, i.e., the genesis and accumulation of beta-amyloid (Abeta) plaques and the formation and accumulation of neurofibrillary tangles in neurons, both of which contribute to neuronal dysfunction and demise. Several genetic studies show that inheritance of a specific IL-1A gene polymorphism increases risk for development of Alzheimer's disease by as much as sixfold. Moreover, this increased risk is associated with earlier age of onset of the disease. Homozygosity for this polymorphism in combination with another in the IL-1B gene further increases risk.
Griffin
W Sue T
WS
Department of Geriatrics, Medicine, and Psychiatry, University of Arkansas for Medical Sciences, Veterans Affairs Medical Center, Little Rock, USA. griffinsuet@uams.edu
Mrak
Robert E
RE
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001253:Astrocytes / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D004314:Down Syndrome / Q000473:pathology; D004827:Epilepsy / Q000378:metabolism / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D017628:Microglia / Q000473:pathology; D008875:Middle Aged; D009410:Nerve Degeneration / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000502:physiology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011110:Polymorphism, Genetic
D016229:Amyloid beta-Peptides; D007375:Interleukin-1; D009419:Nerve Tissue Proteins