Neurofibrillary tau pathology modulated by genetic variation of α -synuclein

Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
Annals of Neurology (Impact Factor: 9.98). 09/2008; 64(3):348-52. DOI: 10.1002/ana.21446
Source: PubMed


We analyzed whether genetic variation of alpha-synuclein modulates the extent of neuropathological changes in a population-based autopsied sample of 272 elderly Finns. None of the 11 markers was associated with the extent of neocortical beta-amyloid pathology. The intron 4 marker rs2572324 was associated with the extent of neurofibrillary pathology (p = 0.0006, permuted p = 0.004; Braak stages IV-VI vs 0-II). The same variant also showed a trend for association with neocortical Lewy-related pathology. These results suggest for the first time that variation of alpha-synuclein modulates neurofibrillary tau pathology and support the recent observations of an interaction of alpha-synuclein and tau in neurodegeneration.

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    • "We used (Supplementary Fig. 1): (i) 288 controls from Finland and 285 controls from Switzerland without neurological conditions, recruited and genotyped for this study; (ii) 1165 USA controls from the Duke Memory study (Need et al., 2009; Cirulli et al., 2010), who consented to participate in epilepsy genetics research; 84% of participants filled in a questionnaire about their history of neurological conditions and the subjects who reported a history of seizures were excluded from the study; (iii) 5667 population controls from the Wellcome Trust Case Control Consortium (2007) Phase 2, September 2009 data release; (iv) 469 population controls from Finland, all 85-years-old or over at the time of recruitment (Vantaa85+) (Myllykangas et al., 2005; Peuralinna et al., 2008); and (v) 211 Irish neurologically-normal controls from the Study of Irish Amyotrophic Lateral Sclerosis (Cronin et al., 2008). "
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    • "We combined results of the population-based Vantaa 85þ study cohort with the hospital-based Helsinki cohort because this large Finnish study only included patients with delirium (cases) without controls. The Vantaa 85þ study [Rahkonen et al., 2001; Peuralinna et al., 2008] is a population based health survey focused on the clinical epidemiology and pathology of dementia and related cognitive disorders. The basic population consisted of all people (n ¼ 601) born before April 1906 living in the city of Vantaa, Southern Finland on April 1991. "
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