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P4‐377: A TOMM40 SNP IN APOE E4 NON‐CARRIERS INCREASES RISK FOR MULTIPLE TYPES OF DEMENTIA
Author(s) -
Tsuang Debby,
Bekris Lynn,
Leverenz James,
Yu ChangEn,
Lopez Oscar,
Hamilton Ronald,
Bennett David,
Schneider Julie,
Buchman Aron,
Larson Eric Berg,
Crane Paul,
Kaye Jeffrey,
Kramer Patricia,
Woltjer Randy,
Trojanowski John Q.,
Weintraub Daniel,
ChenPlotkin Alice,
Schellenberg Gerard D.,
Watson Stennis,
Kulkull Walter,
Nelson Peter T.,
Jicha Gregory A.,
Galasko Douglas,
Masliah Eliezer,
Quinn Joseph,
Chung Kathryn,
Mata Ignacio,
Edwards Karen,
Montine Thomas,
Zabetian Cyrus
Publication year - 2014
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.2014.07.146
Subject(s) - dementia , apolipoprotein e , lewy body , dementia with lewy bodies , allele , single nucleotide polymorphism , disease , alzheimer's disease , parkinson's disease , snp , locus (genetics) , genome wide association study , medicine , psychology , genetics , biology , genotype , gene
tion of 5-HT6 receptor mRNA expression by in situ hybridization we applied theQuantiGeneViewRNAplatform fromAffymetrix.We usedMultiplex analysis to study co-expression of a range of neuronal genes. Frozen sections throughout the brains from male Sprague Dawley rats were hybridized for 5HT6 receptors. Following total mapping, 5-HT6 receptor mRNAvisualization was combined with probes for a range of neurotransmitters or interneuron markers. The sectins were analyzed by bright field and fluorescent microscopy. Results: Detection of target genes was both sensitive and specific. 5-HT6 receptor mRNA was expressed exclusively in neurons. The highest expression levelwas detected inmedium spiny neurons in caudate putamen and in nucleus accumbens, and in the olfactory tubercle. The striatal neurons also expressed GAD67, calbindin and D1/D2 receptors. 5-HT6 mRNA was moderately expressed in hippocampus and throughout cortical regions. These neurons co-expressed the glutamatergic marker vGluT1. Furthermore, weak to moderate expression of cholecystokinin and calbindin mRNAwas detecetd in 5-HT6-receptor-positive cortical and hippocampal neurons. The majority of GAD67positive GABAergic interneurons (in cortex, hippocampus, striatum) did not express 5-HT6 receptor mRNA. However, a weak to moderate signal for 5HT6 receptors was present in a subset of calbindinand calretinin-positive GABAergic interneurons. 5-HT6 receptors did not co-localizewith parvalbumin in forebrain structures. 5-HT6 receptor mRNAwas not expressed in serotonergic, dopaminergic or cholinergic neurons, nor was the receptor co-expressed with somatostatin, VIP or NPY. Conclusions: 5-HT6 receptor mRNA is strongly expressed in GABAergic medium spiny neurons and moderately expressed in glutamatergic neurons. A subset of calretininand calbindin-positive GABAergic interneurons express 5-HT6 receptor mRNA. The present data provide new insights to interpret the mechanism of 5-HT6 receptor signalling.