Common inflammatory mechanisms in Lewy body disease and Alzheimer disease.
Cortical Lewy body disease as a cause of dementia has been recognized for more than 40 years. Only in the past 15 to 20 years, however, has the true frequency of this entity come to be appreciated, primarily because of the advent of sensitive and specific immunohistochemical diagnostic techniques. We now know that there is frequent and extensive overlap, both clinically and pathologically, between Lewy body and Alzheimer diseases. Although some of this overlap may be attributable to common genetic and environmental risk factors, it is also now apparent that the 2 diseases share common neuroinflammatory mechanisms involving activation of microglia, overexpression of interleukin-1 and other inflammatory mediators, and inflammatory toxicity to neurons. Activated microglia are found in association with alpha-synuclein-containing neurons and glia in Parkinson disease, in dementia with Lewy bodies, and in multiple system atrophy, and these associations are reminiscent of microglial associations with neurofibrillary tangle-containing neurons in Alzheimer disease. In vitro and in vivo experimental work has shown reciprocal induction between alpha-synuclein and injured neurons on one hand and activated microglia and cytokine overexpression on the other. These neuroinflammatory processes may be a common link driving progression in both diseases and explaining the frequent overlap between the 2 diseases.
Mrak
Robert E
RE
Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. mrakroberte@uams.edu
Griffin
W Sue T
WS
D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D004660:Encephalitis / Q000209:etiology* / Q000235:genetics; D004777:Environment; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D020961:Lewy Body Disease / Q000150:complications* / Q000235:genetics / Q000266:history; D012307:Risk Factors
D007375:Interleukin-1