title: Risk factor SORL1: from genetic association to functional validation in Alzheimer's disease.
abstract: Alzheimer's disease (AD) represents one of the most dramatic threats to healthy aging and devising effective treatments for this devastating condition remains a major challenge in biomedical research. Much has been learned about the molecular concepts that govern proteolytic processing of the amyloid precursor protein to amyloid-β peptides (Aβ), and how accelerated accumulation of neurotoxic Aβ peptides underlies neuronal cell death in rare familial but also common sporadic forms of this disease. Out of a plethora of proposed modulators of amyloidogenic processing, one protein emerged as a key factor in AD pathology, a neuronal sorting receptor termed SORLA. Independent approaches using human genetics, clinical pathology, or exploratory studies in animal models all converge on this receptor that is now considered a central player in AD-related processes by many. This review will provide a comprehensive overview of the evidence implicating SORLA-mediated protein sorting in neurodegenerative processes, and how receptor gene variants in the human population impair functional receptor expression in sporadic but possibly also in autosomal-dominant forms of AD.
authors.affiliation: Department of Biomedicine, Danish Research Institute of Translational Neuroscience DANDRITE-Nordic EMBL Partnership for Molecular Medicine, Aarhus University, Ole Worms Alle 3, Aarhus C, 8000, Aarhus, Denmark. o.andersen@biomed.au.dk.
authors.forename: Olav M
authors.initials: OM
authors.lastname: Andersen
authors.affiliation: Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13125, Berlin, Germany.
authors.forename: Ina-Maria
authors.initials: IM
authors.lastname: Rudolph
authors.affiliation: Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13125, Berlin, Germany. willnow@mdc-berlin.de.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Willnow
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D012307:Risk Factors
chemical_list: D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human