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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    • "Neurofibrillary tau pathology is modulated by genetic variations of αSyn [54]. Tau phosphorylation is found in synapse-enriched fractions of frontal cortex in PD and AD [55] and in brainstems of αSyn mice [56]. "
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    ABSTRACT: Protein aggregation is a common characteristic of many neurodegenerative disorders, and the interaction between pathological/toxic proteins to cause neurodegeneration is a hot topic of current neuroscience research. Despite clinical, genetic, and experimental differences, evidence increasingly indicates considerable overlap between synucleinopathies and tauopathies or other protein-misfolding diseases. Inclusions, characteristics of these disorders, also occurring in other neurodegenerative diseases, suggest interactions of pathological proteins engaging common downstream pathways. Novel findings that have shifted our understanding in the role of pathologic proteins in the pathogenesis of Parkinson and Alzheimer diseases have confirmed correlations/overlaps between these and other neurodegenerative disorders. The synergistic effects of α-synuclein, hyperphosphorylated tau, amyloid-β, and other pathologic proteins, and the underlying molecular pathogenic mechanisms, including induction and spread of protein aggregates, are critically reviewed, suggesting a dualism or triad of neurodegeneration in protein-misfolding disorders, although the etiology of most of these processes is still mysterious.
    Full-text · Article · Oct 2011 · The Scientific World Journal
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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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    Full-text · Article · Jul 2010 · Brain
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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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    Full-text · Article · Jan 2009 · American Journal of Medical Genetics Part B Neuropsychiatric Genetics
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