Amyloidosis causes downregulation of SorLA, SorCS1 and SorCS3 expression in mice
Author:
Hermey Guido1, Hoffmeister-Ullerich Sabine A.2, Merz Barbara1, Groß Dagmar3, Kuhl Dietmar1, Kins Stefan3
Affiliation:
1. Institute for Molecular and Cellular Cognition, Center for Molecular Neurobiology Hamburg , University Medical Center Hamburg-Eppendorf , D-20251 Hamburg , Germany 2. Bioanalytics, Center for Molecular Neurobiology Hamburg , University Medical Center Hamburg-Eppendorf , D-20251 Hamburg , Germany 3. Division of Human Biology and Human Genetics , University of Kaiserslautern , Erwin-Schrödinger-Straße 13 , D-67663 Kaiserslautern , Germany
Abstract
Abstract
Accumulation of β-amyloid peptide (Aβ) is regarded as a primary cause of Alzheimer’s disease (AD). Aβ is derived by sequential cleavage of the amyloid precursor protein (APP). Alterations in the subcellular targeting of APP are thought to affect the degree of Aβ production. Sorting receptors, such as SorLA, convey subcellular targeting of APP. Dysfunction of SorLA, and likely of the related receptors SorCS1 and SorCS3, cause AD. Nevertheless, disease progression could also provoke altered expression of the receptors. Here, we assessed if Aβ plaque formation promotes altered expression of SorLA, SorCS1 and SorCS3. We analyzed transcript levels during aging and after amyloidosis in brain areas characterized by early amyloid plaque formation in an AD mouse model (APPPS1) and wild types. We observed stable expression levels during aging (1–12 months). After plaque formation, SorCS1 and SorLA expression were markedly reduced in the frontal cerebral cortex and to a minor extent in the hippocampus, whereas SorCS3 expression was solely reduced in the frontal cerebral cortex. Our results indicate that disease progression, associated with Aβ accumulation, can negatively regulate expression of the receptors.
Publisher
Walter de Gruyter GmbH
Subject
Clinical Biochemistry,Molecular Biology,Biochemistry
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