We study the molecular mechanisms of Alzheimer's disease using a variety of approaches, including genetics, immunohistochemistry and cell biology. Only one common genetic risk factor for Alzheimer's disease has been identified so far: APOE. This gene encodes a protein involved in cholesterol transport and cellular repair in the periphery We are exploring these processes in the central nervous system in order to understand how apoE (and lipid metabolism) alters one's risk of Alzheimer's disease. Our current research focuses on the role of cholesterol in the metabolism of the Ab peptide and on the signaling functions of apoE receptors. 

In addition, we are interested in a related dementing illness, amyloid angiopathy. In this condition, the Ab peptide deposits in blood vessels of the brain, leading to gradual dementia or sudden hemorrhagic stroke. We recently identified a mutation in the Ab precursor protein that causes a familial form of amyloid angiopathy. Present studies also include quantitative immunohistological analyses and animal models. 

Selected Publications:

• Pocivavsek A, Rebeck GW. Inhibition of c-Jun N-terminal kinase increases apoE expression in vitro and in vivo. Biochem Biophys Res Commun. July, 2009

• Pocivavsek A, Mikhailenko I, Strickland DK, Rebeck GW. Microglial low-density lipoprotein receptor-related protein 1 modulates c-Jun N-terminal kinase activation. J Neuroimmunol. July 2009

• Hoe HS, Lee KJ, Carney RS, Lee J, Markova A, Lee JY, Howell BW, Hyman BT, Pak DT, Bu G, Rebeck GW. Interaction of reelin with amyloid precursor protein promotes neurite outgrowth. J Neurosci. 29:7459-73, 2009

• Burns MP, Zhang L, Rebeck GW, Querfurth HW, Moussa CE. Parkin promotes intracellular A{beta}1-42 clearance. Hum Mol Genet. 2009

• Rebeck GW. Nontraditional signaling mechanisms of lipoprotein receptors. Sci Signal.  28:2, 2009

• Loane DJ, Pocivavsek A, Moussa CE, Thompson R, Matsuoka Y, Faden AI, Rebeck GW, Burns MP.: Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat Med. 15:377-9, 2009

• Hoe HS, Fu Z, Makarova A, Lee JY, Lu C, Feng L, Pajoohesh-Ganji A, Matsuoka Y, Hyman BT, Ehlers MD, Vicini S, Pak DT, Rebeck GW.  The effects of amyloid precursor protein on postsynaptic composition and activity. J Biol Chem. 284:8495-506, 2009

• Hirata-Fukae C, Li HF, Ma L, Hoe HS, Rebeck GW, Aisen PS, Matsuoka Y.: Levels of soluble and insoluble tau reflect overall status of tau phosphorylation in vivo. Neurosci Lett. 450:51-5, 2009

• Pocivavsek A, Burns MP, Rebeck GW.   Low-density lipoprotein receptors regulate microglial inflammation through c-Jun N-terminal kinase.. Glia. 57:444-53, 2009

• Tractenberg RE, Aisen PS, Hancock GR, Rebeck GW.: No cross-sectional influence of APOE epsilon4 dose on clinical tests in Alzheimer's disease. Neurobiol Aging. 30:1327-8, 2009

• Zhao X, Rebeck GW, Hoe HS, Andrews PM.: Tarenflurbil protection from cytotoxicity is associated with an upregulation of neurotrophins. J Alzheimers Dis. 15:397-407, 2008

• Cartagena CM, Ahmed F, Burns MP, Pajoohesh-Ganji A, Pak DT, Faden AI, Rebeck GW.: Cortical injury increases cholesterol 24S hydroxylase (Cyp46) levels in the rat brain. J Neurotrauma. 25:1087-98, 2008

• Hoe HS, Rebeck GW.: Functional interactions of APP with the apoE receptor family. J Neurochem. 106:2263-71, 2008

• Hirata-Fukae C, Li HF, Hoe HS, Gray AJ, Minami SS, Hamada K, Niikura T, Hua F, Tsukagoshi-Nagai H, Horikoshi-Sakuraba Y, Mughal M, Rebeck GW, LaFerla FM, Mattson MP, Iwata N, Saido TC, Klein WL, Duff KE, Aisen PS, Matsuoka Y.: Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res. 1216:92-103, 2008

• Hoe HS, Rebeck GW.: Regulated proteolysis of APP and ApoE receptors. Mol Neurobiol. 37:64-72, 2008

• Hoe HS, Minami SS, Makarova A, Lee J, Hyman BT, Matsuoka Y, Rebeck GW.: Fyn modulation of Dab1 effects on amyloid precursor protein and ApoE receptor 2 processing. J Biol Chem. 283:6288-99, 2008

• Hoe HS, Cooper MJ, Burns MP, Lewis PA, van der Brug M, Chakraborty G, Cartagena CM, Pak DT, Cookson MR, Rebeck GW.: The metalloprotease inhibitor TIMP-3 regulates amyloid precursor protein and apolipoprotein E receptor proteolysis. J Neurosci. 27:10895-905, 2007

• Eckert GP, Vardanian L, Rebeck GW, Burns MP.: Regulation of central nervous system cholesterol homeostasis by the liver X receptor agonist TO-901317. Neurosci Lett. 423:47-52, 2007

• Czech C, Burns MP, Vardanian L, Augustin A, Jacobsen H, Baumann K, Rebeck GW.: Cholesterol independent effect of LXR agonist TO-901317 on gamma-secretase. J Neurochem. 101:929-36, 2007

• Hoe HS, Freeman J, Rebeck GW.: Apolipoprotein E decreases tau kinases and phospho-tau levels in primary neurons. Mol Neurodegener. 1:18, 2006