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Full-Text Articles in Medicine and Health Sciences

A Functional Polymorphism In The Hmgcr Promoter Affects Transcriptional Activity But Not The Risk For Alzheimer Disease In Swedish Populations., Lina Keller, Charlotte Murphy, Steve Meaney Jul 2010

A Functional Polymorphism In The Hmgcr Promoter Affects Transcriptional Activity But Not The Risk For Alzheimer Disease In Swedish Populations., Lina Keller, Charlotte Murphy, Steve Meaney

Articles

Variations in genes associated with cholesterol homeostasis have been reported to modify the risk of developing Alzheimer disease (AD). To date there have been few investigations into variations in genes directly involved in cholesterol biosynthesis and AD. We investigated the influence of the -911C>A polymorphism (rs3761740) in the hydroxy-methyl-glutaryl CoA reductase (HMGCR) gene promoter on basal and regulated transcription, plasma cholesterol levels and the association with AD. Under in vitro conditions the A allele was found to be significantly more responsive to SREBP-2 mediated regulation than the C allele. In an age and sex matched case-control study, the genotype …


Platelet Alpha- And Beta- Secretase Activities Are Not Significantly Affected By Dementia Or Mild Cognitive Impairment In Swedish Patients., Paul Gorham, Natalie Bark, Steve Meaney, Ingemar Bjorkhem, Milita Crisby Jan 2010

Platelet Alpha- And Beta- Secretase Activities Are Not Significantly Affected By Dementia Or Mild Cognitive Impairment In Swedish Patients., Paul Gorham, Natalie Bark, Steve Meaney, Ingemar Bjorkhem, Milita Crisby

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The processing of the Amyloid Precursor Protein (APP) is a critical event in the formation of amyloid plaques which are composed of the 4kDa amyloid beta-peptide (Abeta). Processing of APP occurs through a non-amyloidogenic pathway, mediated by initial alpha-secretase cleavage or through an amyloidogenic pathway via sequential cleavage by beta- and gamma-secretase enzymes, which produces Abeta peptides. Currently, the diagnosis of probable or possible Alzheimer's disease (AD) is primarily based on neuropsychological and neuroradiological assessment. Recent reports indicate that platelet beta-secretase activity is moderately increased in patients with AD and mild cognitive impairment (MCI). To our knowledge platelet alpha-secretase activity …