 Apolipoprotein E (apoE) plays an important role in the transport of lipoproteins, vitamins, and cholesterol between cells and throughout the circulatory system.
In the human population, the apoE locus is comprised of three major alleles (i.e. apoE2, apoE3, and apoE4) that differ by point mutations at amino acids 112 and 158. Changes at these sites endow apoE with different lipoprotein and apoE receptor binding properties, thereby altering physiological functions that depend on apoE. Consequently, apoE alleles have been associated with alterations in brain and immune function, as well differential risk to cardiovascular disease (CVD) and Alzheimer's disease (AD).
Although more than a decade has passed since apoE4 was identified as the primary genetic risk factor for AD, we are still working as a scientific community to elucidate how apoE4 contributes to AD, and how apoE4-associated risk may be modulated. In addition, the basic functions of apoE in normal brain and the role of apoE in neurodegenerative disease remain unknown. Most of the apoE functions identified both in vitro and in vivo appear to be modulated, if not dependent upon, a distinct set of apoE receptors.
Our lab recently found that human apoE alleles expressed in mice differentially affect synaptic function and signaling in young mice. Ongoing studies are focused on understanding the physiological consequences of human apoE isoforms on synaptic function and behavior, as well as the related biochemical mechanisms.
An additional goal of the NLML is to concentrate multiple investigations on apoE receptors to define how these receptors affect the signaling, metabolism and function of apoE isoforms in the CNS.
For a list of NlML publication related to our Reelein Research Program please click below.
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