Affiliations: Department of Pathology, University of Toledo College of Medicine, Toledo, OH, USA
Correspondence:
[*]
Address for correspondence: Robert E. Mrak, MD, PhD, Department of Pathology, 2280 Dowling Hall, University of Toledo Health Science Campus MS #1090, 3000 Arlington Avenue, Toledo, OH 43614, USA. Tel.: +1 419 383 3469; Fax: +1 419 383 3066; E-mail: [email protected].
Note: [] Communicated by Xiongwei Zhu
Abstract: A role for innate immunity in neurodegenerative diseases is now widely accepted, although debate continues over the relative contributions of these processes to disease progression and/or to disease amelioration. The idea that microglia and cytokines are important in neurodegeneration arose from neuropathological observations, especially in Alzheimer's disease. Microglia are invariant components of the Aβ plaques of Alzheimer's disease, where they show a waxing and waning of numbers, activation state, and cytokine expression during plaque progression. This is in contrast to diffuse Aβ deposits sometimes found in abundance in the brain of non-demented elderly individuals, which do not contain activated microglia. In Alzheimer's disease, plaque-associated astrocytes, which also produce paracrine mediators, show a pattern similar to that of microglia; and the associated plaque progression is accompanied by progressive damage to and loss of adjacent neurons. Further, activated microglia and astrocytes show a progressive pattern of association with neurofibrillary tangles. These observations, together with known functions of the involved cytokines, originally suggested a central role for immunological phenomena in driving disease progression in Alzheimer's disease. Further observations have extended these ideas to α-synuclein-based diseases (Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy) as well as other neurodegenerative diseases and conditions.
