Abstract
The proteolytic breakdown of the amyloid precursor protein (APP) to neurotoxic amyloid-beta peptides in the brain has been recognized as a major pathological pathway in Alzheimer's disease (AD). Yet, the factors that control the processing of APP and their potential contribution to the common sporadic form of AD remain poorly understood. Here, we review recent findings from studies in patients and in animal models that led to the identification of a unique sorting receptor for APP in neurons, designated SORLA/SORL1, that emerges as a key player in amyloidogenic processing and as major genetic risk factor for AD.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease* / genetics
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Alzheimer Disease* / metabolism
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Alzheimer Disease* / pathology
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Amyloid beta-Protein Precursor / genetics
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Amyloid beta-Protein Precursor / metabolism
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Animals
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Animals, Genetically Modified
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Disease Models, Animal
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Humans
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LDL-Receptor Related Proteins / genetics*
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LDL-Receptor Related Proteins / metabolism*
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Membrane Transport Proteins / genetics*
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Membrane Transport Proteins / metabolism*
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Models, Biological
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Neurons / metabolism
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Neurons / pathology
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Protein Transport / genetics
Substances
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Amyloid beta-Protein Precursor
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LDL-Receptor Related Proteins
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Membrane Transport Proteins
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SORL1 protein, human