Our research program is focused on the pathophysiological and therapeutic connections between Alzheimer's disease (AD), diabetes, and cardiovascular disease using transgenic/knockout mouse models. We employ a combination of molecular, cellular, electrophysiological, and behavioral approaches in our research. Current r esearch activities in our laboratory include: 1) Investigation on the role of dietary and/or genetically induced hypercholesterolemia and insulin resistance in the development of AD-like neuropathology and behavior in transgenic mouse models of AD; 2) Potential application and molecular mechanisms of anti-atherogenic and anti-diabetic therapies for the prevention and treatment of AD and other age-related dementia; 3) Modulation of cholesterol and insulin pathways to facilitate synaptic plasticity and cognitive function; 4) Investigation on the role of amyloid-beta peptide in atherogenesis; and 5) Studies on the role of apolipoprotein A-I (apoA-I), a major protein component of the cardio-protective high-density lipoproteins (HDL), and other apolipoproteins in the development of AD.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Neuroscientist. 2023 Jun;29(3):302-316. Microglial TREM2 at the intersection of brain aging and Alzheimer's disease.
- Mol Neurobiol. 2022 Oct 26. doi: 10.1007/s12035-022-03082-0. Deletion of small GTPase H-ras rescues memory deficits and reduces amyloid plaque-associated dendritic spine loss in transgenic Alzheimer's mice.
- Qu W, Li L. Microglial TREM2 at the intersection of brain aging and Alzheimer's disease. Neuroscientist. 2021 Sep 2:10738584211040786.
- Jeong A, Cheng S, Zhong R, Bennett DA, Bergö MO, Li L. Protein farnesylation is upregulated in Alzheimer's human brains and neuron-specific suppression of farnesyltransferase mitigates pathogenic processes in Alzheimer's model mice. Acta Neuropathol Commun. 2021 Jul 27;9(1):129.
- Qu W, Li L. Loss of TREM2 confers resilience to synaptic and cognitive impairment in aged mice. J Neurosci. 2020 Dec 9;40(50):9552-9563.
- Qu W, Suazo KF, Liu W, Cheng S, Jeong A, Hottman D, Yuan LL, Distefano MD, Li L. Neuronal protein farnesylation regulates hippocampal synaptic plasticity and cognitive function. Mol Neurobiol. 2021 Mar;58(3):1128-1144.
- Chernick D, Ortiz-Valle S, Jeong A, Qu W, Li L. Peripheral versus central nervous system APOE in Alzheimer's disease:Interplay across the blood-brain barrier. Neurosci Lett. 2019 Jun 7:134306.
- Hottman D, Cheng S, Gram A, LeBlanc K, Yuan LL, Li L. Systemic or forebrain neuron-specific deficiency of geranylgeranyltransferase-1 impairs synaptic plasticity and reduces dendritic spine density. Neuroscience. 2018 Mar 1;373:207-217.
- Cheng S, Wani WY, Hottman DA, Jeong A, Cao D, LeBlanc KJ, Saftig P, Zhang J, Li L. Haplodeficiency of cathepsin D does not affect cerebral amyloidosis and autophagy in APP/PS1 transgenic mice. J Neurochem. 2017;142:297-304.
- Li D, Thomas R, Tsai MY, Li L, Vock DM, Greimel S, Yu F. Vascular biomarkers to predict response to exercise in Alzheimer's disease: the study protocol. BMJ Open. 2016 Dec 30;6(12):e011054.
- Segrest JP, Jones MK, Catte A, Manchekar M, Datta G, Zhang L, Zhang R, Li L, Patterson JC, Palgunachari MN, Oram JF, Ren G. Surface density-induced pleating of a lipid monolayer drives nascent high density lipoprotein assembly. Structure 2015;23(7):1214-1226.
- Li Y, Mair DC, Schuller RM, Li L, Wu J. Genetic mechanism of human neutrophil antigen 2 deficiency and expression variations. PLOS Genetics. 2015; 11(5):e1005255.
- Wu J, Li L. Autoantibodies in Alzheimer's disease: potential biomarkers, pathogenic roles, and therapeutic implications. J Biomed Res. 2016;30:361-372.
- Chen Y, Peng Y, Che, P, Gannon M, Liu Y, Li L, Bu G, van Groen T, Jiao, K, Wang Q. α2A adrenergic receptor promotes amyloidogenesis through disrupting APP-SorLA interaction. Proc Nat Acad Sci USA. 2014;111(48):17296-17301.
- Hottman DA, Chernick D, Cheng S, Wang Z, Li L. HDL and cognition in neurodegenerative disorders. Neurobiol Dis. 2014;72:22-36.
- Cheng S, LeBlanc K, Li L. Triptolide preserves cognitive function and reduces neuropathology in a mouse model of Alzheimer's disease. PLOS One. 2014;9(10): e108845.
- Wood WG, Li L, Muller WE, Eckert GP. Cholesterol as a causative factor in Alzheimer's disease: a debatable hypothesis. J Neurochem. 2014;129:559-572
- Parent M, Hottman DA, Cheng S, Zhang W, McMahon LL, Yuan L, Li L. Simvastatin treatment enhances NMDAR-mediated synaptic transmission by upregulating the surface distribution of the GluN2B subunit. Cell Mol Neurobiol. 2014;34:693-705.
Current Graduate Students:
Wenhui Qu (Neuroscience, University of Minnesota).