Laboratory of Aging and Neurodegeneration

The Rebeck Lab studies the molecular mechanisms of Alzheimer's disease using a variety of approaches, including animal models, biochemistry, immunohistochemistry, and cell biology.

We focus on the strongest genetic risk factor for Alzheimer’s disease: APOE. This gene encodes a protein involved in cholesterol transport and cellular repair. There are three common alleles of APOE: APOE3, which is the most common form of APOE; APOE2, which lowers the risk of Alzheimer’s disease by 50%; and APOE4, which increases the risk by 300%. We are exploring the roles of APOE in the normal regulation of cholesterol metabolism and inflammation in the central nervous system. For this work, we are examining neurons and glia in culture, to look at normal regulation and metabolism of APOE. We are examining the structure of the APOE protein, and its post-translational modifications and association with brain lipoproteins. We are examining mouse models in which the mouse APOE was replaced by the human forms of APOE, studying their brain structure, biochemistry, and behavior. In these various studies, we are interested in the pharmacologic rescue of the effects of APOE4, particularly focusing on drugs that affect cholesterol metabolism or reduce inflammation. Using the APOE knock-in mouse model, we are also examining how the adverse effects of APOE genotype interact with the adverse effects of metabolic disturbance (obesity, diabetes) and of cancer chemotherapy (cancer chemotherapy-induced cognitive impairment).

Our goals are to understand why APOE affects the risk of Alzheimer’s disease so strongly, and to define what can be done to lower one’s risk prior to the onset of clinical signs.

Research Funding

NIH R01 NS100714 (Rebeck, PI) 08/15/2017 – 05/31/2022

Effects of APOE isoform structures on normal brain function

NIH R01 AG067258 (Rebeck, PI) 05/15/2020 - 01/31/2025

APOE4 promotes pathogenesis in a mouse model of cancer chemotherapy induced cognitive impairment

NIH R01 AG067258-01S1 (Rebeck, mentor) 07/01/2021 – 06/30/2023

Diversity supplement to support PhD training of Jordy Sepulveda

NIH R21 AG074139-01 (Rebeck, PI) 08/01/2021 – 04/30/2023

Synergistic effect of APOE genotype and obesity in CNS inflammation and risk of Alzheimer's disease.

NIH T32 AG071745-01 (Rebeck, PI) 09/15/2021 – 08/31/2026

Aging and Alzheimer’s Research Training