title: Deletion of Crry, the murine ortholog of the sporadic Alzheimer's disease risk gene CR1, impacts tau phosphorylation and brain CFH.
abstract: Large-scale genome-wide SNP association studies have identified an association between variants of CR1, the gene encoding complement component receptor 1, and the sporadic form of Alzheimer's disease. The role of CR1 and the complement system in Alzheimer's disease remains far from clear. In rodents the closest ortholog of CR1 is the Crry gene (Cr1-related protein Y). To begin to explore its role in Alzheimer's disease we examined hippocampal lysates from Crry(-/-) mice and age matched controls by immunoblotting. We measured complement factor H, a component of the complement system and biomarker for Alzheimer's disease progression, and tau phosphorylation at the serine 235 site, hyperphosphorylated forms of tau being a defining neuropathological hallmark of the disease. We found that levels of CFH and of tau phosphorylation at serine 235 were strongly and significantly reduced in Crry(-/-) samples. These observations provide a starting point for further attempts to determine the role of CR1 in the neuropathological process driving Alzheimer's disease.
authors.affiliation: King's College London, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK. Richard.1.Killick@kcl.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: Killick
authors.forename: T R
authors.initials: TR
authors.lastname: Hughes
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
authors.forename: S
authors.initials: S
authors.lastname: Lovestone
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D017242:Complement Factor H / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D011951:Receptors, Complement / Q000235:genetics*; D017463:Receptors, Complement 3b / Q000235:genetics*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C509991:CR1 protein, human; C081470:Cr1l protein, mouse; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D016875:tau Proteins; D017242:Complement Factor H