Interleukin-1 beta: a common cause of Alzheimer's disease and diabetes mellitus.
Alzheimer disease is characterized by the presence of beta-amyloid protein deposits, neurofibrillary tangles and cholinergic dysfunction throughout the hippocampal region. In addition, the hippocampus, hypothalamus and olfactory bulb--the three areas where the insulin receptors are most dense--are also subject to neurodegeneration. The exact cause of the beta-amyloid deposits and NFTs is unknown. However, it is our intention to explicate the various pathogenic pathways through which Alzheimer disease arises. Fundamentally, the structural and metabolic damage found in Alzheimer disease is due to sustained elevation of interleukin-1 beta, a feature which is also found in insulin-dependent diabetes mellitus. Similarly, the beta-AP deposits found in the Alzheimer brain share the same molecular structure as the amylin deposits found in the pancreatic beta-cells in non-insulin-dependent diabetes mellitus (NIDDM), and are equally neurotoxic. These, and other pathophysiological parallels, afford some insight into the probably cause of Alzheimer disease and, as such, forms the basis of the causal hypothesis advanced in this paper.
Holden
R J
RJ
Medical Research Unit, University of Wollongong, NWS, Australia.
Mooney
P A
PA
D000544:Alzheimer Disease / Q000209:etiology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003920:Diabetes Mellitus / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007375:Interleukin-1 / Q000502:physiology*; D008954:Models, Biological; D016874:Neurofibrillary Tangles / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D016207:Cytokines; D007328:Insulin; D007375:Interleukin-1; D001708:Biopterins; C003402:sapropterin