BACKGROUND: Genetic, epidemiologic, and biochemical evidence suggests that apolipoprotein E, low-density lipoprotein receptors, and lipid metabolism play important roles in sporadic Alzheimer disease (AD). OBJECTIVE: To identify novel candidate genes associated with sporadic AD. DESIGN: We performed an unbiased microarray screen for genes differentially expressed in lymphoblasts of patients with sporadic AD and prioritized 1 gene product for further characterization in AD brain. SETTING: Emory University, Atlanta, Ga. SUBJECTS: Cell lines were used from 14 patients with AD and 9 normal human control subjects. RESULTS: Six genes were differentially expressed in lymphoblasts of 2 independent groups of patients with probable AD and autopsy-proven AD. We hypothesized that 1 of the genes, termed low-density lipoprotein receptor relative with 11 binding repeats (LR11) (reduced 1.8- and 2.5-fold in AD lymphoblasts vs controls), might be associated with sporadic AD on the basis of its function as neuronal apolipoprotein E receptor. We found dramatic and consistent loss of immunocytochemical staining for LR11 in histologically normal-appearing neurons in AD brains. This reduction of LR11 protein was confirmed by quantitative Western blotting (P =.01). CONCLUSIONS: There is loss of the microarray-derived candidate, LR11, in neurons of AD brains. This study shows that microarray analysis of widely available lymphoblasts derived from patients with AD holds promise as a primary screen for candidate genes associated with AD.
BACKGROUND: Genetic, epidemiologic, and biochemical evidence suggests that apolipoprotein E, low-density lipoprotein receptors, and lipid metabolism play important roles in sporadic Alzheimer disease (AD). OBJECTIVE: To identify novel candidate genes associated with sporadic AD. DESIGN: We performed an unbiased microarray screen for genes differentially expressed in lymphoblasts of patients with sporadic AD and prioritized 1 gene product for further characterization in AD brain. SETTING: Emory University, Atlanta, Ga. SUBJECTS: Cell lines were used from 14 patients with AD and 9 normal human control subjects. RESULTS: Six genes were differentially expressed in lymphoblasts of 2 independent groups of patients with probable AD and autopsy-proven AD. We hypothesized that 1 of the genes, termed low-density lipoprotein receptor relative with 11 binding repeats (LR11) (reduced 1.8- and 2.5-fold in AD lymphoblasts vs controls), might be associated with sporadic AD on the basis of its function as neuronal apolipoprotein E receptor. We found dramatic and consistent loss of immunocytochemical staining for LR11 in histologically normal-appearing neurons in AD brains. This reduction of LR11 protein was confirmed by quantitative Western blotting (P =.01). CONCLUSIONS: There is loss of the microarray-derived candidate, LR11, in neurons of AD brains. This study shows that microarray analysis of widely available lymphoblasts derived from patients with AD holds promise as a primary screen for candidate genes associated with AD.
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Authors: Iris K Salgado; Melissa Serrano; José O García; Namyr A Martínez; Héctor M Maldonado; Carlos A Báez-Pagán; José A Lasalde-Dominicci; Walter I Silva Journal: Cell Mol Neurobiol Date: 2011-11-30 Impact factor: 5.046
Authors: Anja W Fjorback; Matthew Seaman; Camilla Gustafsen; Arnela Mehmedbasic; Suzanne Gokool; Chengbiao Wu; Daniel Militz; Vanessa Schmidt; Peder Madsen; Jens R Nyengaard; Thomas E Willnow; Erik Ilsø Christensen; William B Mobley; Anders Nykjær; Olav M Andersen Journal: J Neurosci Date: 2012-01-25 Impact factor: 6.167
Authors: Ross W Paterson; Jamie Toombs; Catherine F Slattery; Jonathan M Schott; Henrik Zetterberg Journal: Mol Diagn Ther Date: 2014-04 Impact factor: 4.074