Variation in the LRP-associated protein gene (LRPAP1) is associated with late-onset Alzheimer disease
AMERICAN JOURNAL OF MEDICAL GENETICS
Authors: Sanchez, L; Alvarez, V; Gonzalez, P; Gonzalez, I; Alvarez, R; Coto, E
Abstract
The LRP-associated protein is involved in the amount of mature LRP expressed on liver and brain. ERP is the main ApoE receptor and also binds alpha2-macroglobulin (alpha 2M), a protein that associates with the beta -amyloid protein (betaA). By binding to alpha 2M, LRP is responsible for the clearance of secreted betaA, thus preventing fibril formation. Genetic variation at the APOE, A2M, and LRP genes has been associated with the risk of developing late-onset Alzheimer disease (LOAD). We genotyped 373 patients, 300 controls, and 100 healthy elderly controls for a common DNA-polymorphism at the LRPAP1 gene (Insertion/Deletion, intron 5). Homozygotes for the rare Insertion (I) allele were at a significantly lower frequency in patients compared with controls (P = 0.002; OR = 0.29; 95% CI = 0.13, 0.68), and in patients compared with healthy elderly controls (P = 0.0002; OR = 0.18; 95% CI = 0.07, 0.46). No patient with an age at the onset below 75 years was II (0 of 214) compared with 8 in the group above 75 years (8 of 159) (P = 0.0044), suggesting that this genotype delays the onset of the disease. According to our data, the variation at the LRPAP1 gene is associated with the risk of developing LOAD. This is in agreement with the role of the LRPAP1 protein in the amyloidogenic pathway. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 105: 76-78, 2001. (C) 2001 Wiley-Liss, Inc.
Differential protein expression in chicken macrophages and heterophils in vivo following infection with Salmonella Enteritidis
VETERINARY RESEARCH
Authors: Sekelova, Zuzana; Stepanova, Hana; Polansky, Ondrej; Varmuzova, Karolina; Faldynova, Marcela; Fedr, Radek; Rychlik, Ivan; Vlasatikova, Lenka
Abstract
In this study we compared the proteomes of macrophages and heterophils isolated from the spleen 4 days after intravenous infection of chickens with Salmonella Enteritidis. Heterophils were characterized by expression of MMP9, MRP126, LECT2, CATHL1, CATHL2, CATHL3, LYG2, LYZ and RSFR. Macrophages specifically expressed receptor proteins, e. g. MRC1L, LRP1, LGALS1, LRPAP1 and a DMBT1L. Following infection, heterophils decreased ALB and FN1, and released MMP9 to enable their translocation to the site of infection. In addition, the endoplasmic reticulum proteins increased in heterophils which resulted in the release of granular proteins. Since transcription of genes encoding granular proteins did not decrease, these genes remained continuously transcribed and translated even after initial degranulation. Macrophages increased amounts of fatty acid elongation pathway proteins, lysosomal and phagosomal proteins. Macrophages were less responsive to acute infection than heterophils and an increase in proteins like CATHL1, CATHL2, RSFR, LECT2 and GAL1 in the absence of any change in their expression at RNA level could even be explained by capturing these proteins from the external environment into which these could have been released by heterophils.