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S1‐02‐01: Experimental models of LRRK2 dysfunction in Parkinson's disease
Author(s) -
Moore Darren J.
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.188
Subject(s) - lrrk2 , gtpase , biology , transgene , kinase , microbiology and biotechnology , mutant , protein kinase domain , alpha synuclein , parkinson's disease , genetics , gene , mutation , disease , medicine , pathology
metabolic risk states, which may precede or result from underlying dementiarelated neuropathologies. This is exemplified during the prodromal phase of dementia, as vascular and metabolic parameters decline in relation to dementia development, and potentially in a different way from ‘normal’ aging. While published reports discuss mid-life and late-life relationships between vascular risk factors and dementia, continuous data from longitudinal studies also point to a natural history of vascular and metabolic parameters in relationship to dementia onset. New genetic findings enrich the evidence base for a vascular and metabolic etiology, as well as provide a broader evidence base for potential involvement of peripheral metabolism in health of the brain. Methods: To evaluate the epidemiologic evidence for vascular and metabolic risk in dementia etiology and progression, a review of the epidemiologic literature is provided. Longitudinal population data are presented from different ages and stages of adult life to illustrate the evolutionary role of these factors in dementia. Potential biological mechanisms are discussed. Results: Studies suggest that the combined influence of vascular and metabolic factors contribute to risk and progression of dementia. Traditional vascular risk factors mediate their effects not only through effects on the vasculature, but via their roles in altering metabolism. In addition, neuropathologies accompanying dementia influence key regulatory axes modulating vascular and metabolic risk. Conclusions: Dementia is a disorder involving both brain and periphery and including both vascular and metabolic risk components.