Members of the low-density lipoprotein (LDL) receptor gene family have a diverse set of biological functions that transcend lipid metabolism. Lipoprotein receptors have broad effects in both the developing and adultbrain and participate in synapse development, cargo trafficking, and signal transduction. In addition, several family members play key roles in Alzheimer's disease (AD) pathogenesis and neurodegeneration. This Review summarizes our current understanding of the role lipoprotein receptors play in CNS function and AD pathology, with a special emphasis on amyloid-independent roles in endocytosis and synaptic dysfunction. The low-density lipoprotein receptors have diverse biological functions that transcend lipid metabolism. Lane-Donovan, Philips, and Herz review current understanding of lipoprotein receptor function in the CNS and AD pathology, with an emphasis on amyloid-independent roles in endocytosis and synaptic dysfunction.
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