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.
MeSH terms
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Aged, 80 and over
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Brain / metabolism
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Brain / pathology*
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Brain / physiopathology
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Cohort Studies
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DNA Mutational Analysis
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Female
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Genetic Markers / genetics
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Genetic Predisposition to Disease / genetics
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Genetic Testing
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Genetic Variation / genetics
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Humans
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Lewy Bodies / genetics
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Lewy Bodies / metabolism
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Lewy Bodies / pathology
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Male
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Neocortex / metabolism
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Neocortex / pathology
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Neocortex / physiopathology
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Nerve Degeneration / genetics
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Nerve Degeneration / metabolism
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Nerve Degeneration / pathology
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Neurodegenerative Diseases / genetics*
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Neurodegenerative Diseases / metabolism
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Neurodegenerative Diseases / pathology*
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Neurofibrillary Tangles / genetics
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Neurofibrillary Tangles / metabolism
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Neurofibrillary Tangles / pathology*
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Neurons / metabolism
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Neurons / pathology*
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alpha-Synuclein / genetics*
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tau Proteins / metabolism*
Substances
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Genetic Markers
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alpha-Synuclein
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tau Proteins