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P3–174: The regional distribution and magnitude of the pathology in Alzheimer disease correlate with the regional pattern and intensity of the aminergic innervation of the forebrain
Author(s) -
Schmitt Horst P.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1442
Subject(s) - brainstem , pathology , neuroscience , biology , forebrain , serotonergic , medicine , receptor , central nervous system , serotonin
pathogenesis of several disorders since autopsy results of mutation carriers revealed diverse brain pathologies including pathology resembling Alzheimer Disease (AD). The domain structure of the LRRK2 protein suggests a wide variety of functions that could be responsible for the pleomorphic brain neuropathology of mutation carriers. Intriguingly LRRK2 is mapped to a chromosome 12 locus, linked to late-onset familial AD and thus LRRK2 represents a good positional and functional gene candidate for AD. Objective(s): To elucidate the genetic contribution of LRRK2 in a Canadian PD dataset and to conduct association studies to test the hypothesis that four common coding LRRK2 polymorphisms might be associated with increased susceptibility to AD. Methods: We are using our DNA microarray system to perform a complete mutational survey of LRRK2 in a PD dataset consisting of 72 probands of families with PD. The genotypes for four common LRRK2 single nucleotide polymorphisms were obtained in three independent late-onset AD datasets: North American sporadic casecontrol set (243 AD cases and 252 normal controls); and two expanded groups of AD families (124 North European and 118 Caribbean Hispanic pedigrees). Results: For the AD association studies we selected four coding variations, located in three different functional LRRK2 domains (LRR, Ras, WD40): L953L (rs7966550)-14kb-H1398R (rs7133914)-11kbG1624G (rs1427263)-45kb-T2397M (rs3761863). The results of the microarray screen for mutations in PD and the association studies in AD are currently under analysis and will be presented.