Neurofibrillary tau pathology modulated by genetic variation of alpha-synuclein.
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.
Peuralinna
Terhi
T
Molecular Neurology Programme, Biomedicum, University of Helsinki, Helsinki, Finland.
Oinas
Minna
M
Polvikoski
Tuomo
T
Paetau
Anders
A
Sulkava
Raimo
R
Niinistö
Leena
L
Kalimo
Hannu
H
Hernandez
Dena
D
Hardy
John
J
Singleton
Andrew
A
Tienari
Pentti J
PJ
Myllykangas
Liisa
L
D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D016631:Lewy Bodies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D019579:Neocortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D051844:alpha-Synuclein / Q000235:genetics*; D016875:tau Proteins / Q000378:metabolism*
D005819:Genetic Markers; D051844:alpha-Synuclein; D016875:tau Proteins