title: Knowing me, knowing you: can a knowledge of risk factors for Alzheimer's disease prove useful in understanding the pathogenesis of Parkinson's disease?
abstract: Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative disorders. Why some individuals develop one disease rather than the other is not clear. Association studies with a case-control design are the time-honored approach to identifying risk factors. Extensive association studies have been carried out in both diseases creating a large knowledge database, however, reproducible risk factors remain rare. This general lack of knowledge of pathogenesis prevents us from reducing the worldwide burden of these diseases. Case-control studies are reductionist paradigms that assume, for maximum power, that the two populations being compared are exclusive and homogenous. The common occurrence of incidental AD and PD-type pathology combined with 'intermediate phenotypes' such as dementia with Lewy bodies suggest that aging itself, AD, and PD are part of a complex continuum characterized by variable amounts of amyloid-β, tau, and α-synuclein pathology. This heterogeneity may be a contributor to the lack of reproducibility in association studies to date. Here, we speculate on alternative experimental approaches to the case-control paradigm and consider how the association-study literature for AD and PD might be re-interpreted in terms of a disease spectrum.
authors: Discipline of Pathology, Sydney Medical School, University of Sydney, Sydney, NSW, Australia. g.sutherland@sydney.edu.au
authors: Greg T
authors: GT
authors: Sutherland
authors: Gerhard A
authors: GA
authors: Siebert
authors: Jillian J
authors: JJ
authors: Kril
authors: George D
authors: GD
authors: Mellick
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000150:complications; D006801:Humans; D019359:Knowledge; D008954:Models, Biological; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology*; D010575:Pesticides / Q000633:toxicity; D010641:Phenotype; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking
chemical_list: D010575:Pesticides