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lüll The neuronal sortilin-related receptor gene SORL1 and late-onset Alzheimer s disease Lee JH; Barral S; Reitz CCurr Neurol Neurosci Rep 2008[Sep]; 8 (5): 384-91Recent studies indicate that two clusters of single nucleotide polymorphisms in the neuronal sortilin-related receptor gene (SORL1) are causally associated with late-onset Alzheimer's disease (AD). At the cellular level, SORL1 is thought to be involved in intracellular trafficking of amyloid precursor protein. When this gene is suppressed, toxic amyloid beta production is increased, and high levels of amyloid betaare associated with a higher AD risk. Extending the cellular findings, gene expression studies show that SORL1 is differentially expressed in AD patients compared with controls. Furthermore, several genetic studies have identified allelic and haplotypic SORL1 variants associated with late-onset AD, and these variants confer small to modest risk of AD. Taken together, the evidence for SORL1 as a causative gene is compelling. However, putative variants have not yet been identified. Further research is necessary to determine its utility as a diagnostic marker of AD or as a target for new therapeutic approaches.|Age of Onset[MESH]|Aged[MESH]|Alleles[MESH]|Alzheimer Disease/epidemiology/*genetics/metabolism[MESH]|Amyloid beta-Protein Precursor/metabolism[MESH]|Chromosome Mapping[MESH]|Endosomes/physiology[MESH]|Gene Expression Profiling[MESH]|Genetic Predisposition to Disease[MESH]|Haplotypes/genetics[MESH]|Humans[MESH]|LDL-Receptor Related Proteins/*genetics/physiology[MESH]|Membrane Transport Proteins/*genetics/physiology[MESH]|Polymorphism, Single Nucleotide[MESH]|Protein Transport[MESH]|Risk[MESH]|trans-Golgi Network/physiology[MESH] |