Neurofibrillary tau pathology modulated by genetic variation of α -synuclein

Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
Annals of Neurology (Impact Factor: 11.91). 09/2008; 64(3):348-52. DOI: 10.1002/ana.21446
Source: PubMed

ABSTRACT 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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POLG1 geenin polyQ-jakson non-10Q pituusvariantit näyttävät lisäävän PT:n riskiä. Aineistossamme ei löytynyt assosiaatiota DJ-1 tai parkin geeneihin, joiden mutaatiot aiheuttavat resessiivisen varhain alkavan PT:n. Myöskään COMT-entsyymin aktiivisuuteen vaikuttava COMT Val158Met substituutio tai Ala72Ser eivät olleet yhteydessä PT:n riskiin. APOE e2/3/4 polymorfismin tiedetään vaikuttavan mm. Alzheimerin taudin riskiin ja aivovamman ennusteeseen, samoin APOE promoottorialueen polymorfismien ja haplotyyppien yhteys Alzheimer-riskiin on raportoitu. Aineistossamme APOE e2/3/4 ei assosioitunut PT riskiin, eivät myöskään -219G/T, +113G/C polymorfismit tai APOE haplotyypit.