{"id":4134,"date":"2016-08-29T16:39:31","date_gmt":"2016-08-29T20:39:31","guid":{"rendered":"http:\/\/www.bu.edu\/biology\/?post_type=profile&p=4134"},"modified":"2026-04-23T15:23:52","modified_gmt":"2026-04-23T19:23:52","slug":"beffert","status":"publish","type":"profile","link":"https:\/\/www.bu.edu\/biology\/people\/profiles\/beffert\/","title":{"rendered":"Uwe Beffert"},"content":{"rendered":"

Lab Website<\/a>CV<\/a><\/p>\n

Current Research<\/h3>\n

Our lab investigates the role of genetic risk factors such as apolipoprotein E (apoE) in Alzheimer\u2019s disease (AD). AD is a progressive neurodegenerative disease and the leading cause of dementia in the elderly, characterized pathologically by the loss of synapses and neurons as well as the formation of extracellular amyloid plaques and intracellular neurofribrillary tangles. The \u03b54 allele of apoE is the most important genetic risk factor for late-onset sporadic Alzheimer\u2019s disease (LOAD). ApoE is a secreted glycoprotein that binds to a number of single-pass transmembrane receptors of the low-density-lipoprotein (LDL) receptor family, including apoER2 (LRP8), VLDLR, LDL receptor, LRP1 and TREM2 to mediate functions through intracellular signaling and endocytosis. In humans, apoE is polymorphic giving rise to three major alleles with frequencies of about 8% for \u03b52, 77% for \u03b53 and 15% for \u03b54 in the general population. In LOAD, apoE \u03b54 allele frequency increases to about 40% and individuals with one \u03b54 allele are 3 to 4 times more likely to develop AD than those without an \u03b54 allele. The goal of our lab is to understand the biochemical and functional relationship between apoE ligands and their respective receptors in the brain, ultimately to provide mechanistic understanding as to why the \u03b54 allele of apoE confers increased risk for Alzheimer\u2019s disease and to provide plausible pathways to treatment.<\/p>\n

Another area of investigation relates to the role of the LDL receptor family in neuronal migration and brain development. Like apoE, Reelin is a ligand for several LDL receptor family members and plays a critical role in determining the final positioning of neurons in the brain. Our work has uncovered key roles for Reelin in intracellular signaling as well as critical roles for cytoskeletal proteins to rearrange the neuronal cytoskeleton during neuronal migration. The goal of this area of research is to understand the role of ligands such as Reelin in the process of brain development and ultimately how alterations of this process may affect behavior in developmental diseases such as autism and schizophrenia.<\/p>\n

Selected Publications<\/h3>\n