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.)
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 Jul 7; 23(7):1214-26. PMID: 26095027 PMCID: PMC4496276
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. 2015; in press.
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 Dec 2;111(48):17296-301.
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 Disease: A Debatable Hypothesis. J Neurochem. 2014;
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(5):693-705.
Wood WG, Li L, Müller WE, Eckert GP. Cholesterol as a causative factor in Alzheimer's disease: a debatable hypothesis. J Neurochem. 2013 Dec 12;.
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's Disease. J Biol Chem 2013;
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 Neuroinflammation 2012 Jan 18; in press.
Li L, Li S, Jones MK, Segrest JP. Rotational and hinge dynamics of discoidal high density lipoproteins probed by interchain disulfide bond formation. 2011. Biochimica Biophysica Acta 2011 Oct 19. [Epub ahead of print]; in press.
Akhter H, Katre A, Li L, Liu X, Liu RM. Therapeutic potential and anti-amyloidosis mechanisms of tert-butylhydroquinone for Alzheimer’s disease. J Alzheimers Dis 2011; 26(4):767-78.
Lewis TL, Cao D, Lu H, Mans RA, Su YR, Jungbauer L, Linton MF, Fazio S, Ladu MJ, Li L. Overexpression of human apolipoprotein A-I preserves cognitive function and attenuates neuroinflammation and cerebral amyloid angiopathy in a mouse model of Alzheimer's disease. J Biol Chem . 2010 Sep 16.
Mans RA, Chowdhury N, Cao D, McMahon L, Li L . Simvastatin enhances hippocampal long-term potentiation in C57BL/6 mice . Neuroscience 2010; 166:435-44.
Gu F, Jones MK, Chen J, Catte A, Patterson JC, Jerome WG, Li L *, Segrest JP*. Structures of discoidal high density lipoproteins: a combined computational-experimental approach . J Biol Chem. 2010;285(7):4652-65. (*Co-corresponding authors).
Liu RM, van Groen T, Katre A, Cao D, Kadisha I, Ballinger C, Carroll, SL, Wang L, Li L . Knockout of plasminogen activator inhibitor 1 gene reduces amyloid beta peptide burden in a mouse model of Alzheimer's disease . Neurobiol Aging 2009; in press.
Handattu SP, Garber DW, Monroe CC, van Groen T, Kadish I, Nayyar G, Cao D, Palgunachari MN, Li L , Anantharamaiah GM. Oral apolipoprotein A-I mimetic peptide improves cognitive function and reduces amyloid burden in a mouse model of Alzheimer's disease . Neurobiol Dis. 2009; 34:525-534.
Li L , Cao D, Desmond R, Rahman A, Lah JJ, Levey AI, Zamrini E. Cognitive performance and plasma levels of homocysteine, vitamin B12, folate, and lipids in patients with Alzheimer's disease . Dement Geriatr Cogn Disord. 2008; 26:384-390.
Li L , Weng W, Fisher EA. Plasma carboxyl ester lipase activity modifies apoB-lipoprotein composition and turnover but has no effect on atherosclerosis in a transgenic mouse model . Metabolism. 2008; 57:1361-68.
Jin J, Kim H, Maxwell JA, Li L , Fukuchi K. Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer's disease . J Neuroinflammation 2008; 5:23.