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.)
- 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 Nov 2:JN-RM-2193-20.
- 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. 2020 Oct 24. doi: 10.1007/s12035-020-02169-w.
- 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.
- Cheng S, Cao D, Hottman DA, Yuan L, Bergo MO, Li L. Farnesyltransferase haplodeficiency reduces neuropathology and rescues cognitive function in a mouse model of Alzheimer disease. J Biol Chem. 2013;288:35952-35960.
- Mans RA, McMahon L, Li L.Simvastatin-mediated enhancement of long-term potentiation is driven by farnesyl-pyrophosphate depletion and inhibition of farnesylation. Neuroscience. 2012;202:1-9.
- Kou J, Song M, Pattanayak A, Lim JE, Yang J, Cao D, Li L, Fukuchi K. Combined treatment of Aβ immunization with statin in a mouse model of Alzheimer's disease J Neuroimmunol. 2012;244(1-2):70-83.
- Li L, Li S, Jones MK, Segrest JP. Rotational and hinge dynamics of discoidal high density lipoproteins probed by interchain disulfide bond formation. Biochim Biophys Acta. 2012;1821:481-489.
Current Graduate Students:
Wenhui Qu (Neuroscience, University of Minnesota).