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Unraveling the Role of Immune Pathways in Alzheimer’s Disease

Weekly Seminar
Who Should Attend: 


Guest Speaker
Bruce T. Lamb, Ph.D.
Executive Director
Stark Neurosciences Research Institute
Medical and Molecular Genetics
Roberts Family Chair in Alzheimer's Disease Research


The primary focus of my laboratory is to utilize transgenic mice to study the molecular basis of neurodegeneration, including AD. More specifically, we have developed and characterized genetic models of neurodegeneration by introducing different human genes carrying disease-causing mutations into mice. Importantly, we have demonstrated that these mice develop numerous biochemical, behavioral and neuropathological features of AD and neurodegeneration. We have been continuing to generate additional models and characterize these mice in terms of molecular biological, biochemical, behavioral, and neuropathological criteria that will help us determine the effect of these neurodegenerative disease gene mutations on in vivo biological function and dysfunction. It has become increasing clear that innate immune pathways are involved in AD pathogenesis, which has been a more recent focus of the laboratory. Notably, my laboratory has observed that neuronal-microglial communication through the chemokine fractalkine (CX3CL1) and its cognate receptor, CX3CR1, plays a critical role in AD with opposing effects on the development of the Aβ and microtubule-associated protein tau pathology observed in AD. Furthermore, my laboratory has begun to examine the role of TBI as an environmental risk factor for neurodegeneration and observed a unique neuroinflammatory response in a mouse model of AD exposed to TBI. Finally, in recent pioneering studies, my laboratory has demonstrated that deficiency for TREM2 ameliorates β-amyloid (Aβ) pathology, and lowers expression of inflammatory mediators in an AD mouse model. These provocative findings suggests that TREM2 is essential for accumulation of TREM2+ myeloid cells around Aβ deposits and that these cells express markers consistent with their derivation from peripheral, infiltrating monocytes. 

Bruce Lamb Figure

Figure from Jay et al, 2015. In the APPPS1 mouse model of AD, TREM2 colocalized with CD45 around amyloid deposits but not P2RY12. All experiments used n = 7–8 mice per group, and at least two independent experiments were performed for all analyses.


Lee, S., Xu, G., Jay, T.R., Bhatta, S., Kim, K.W., Jung, S., Landreth, G.E., Ransohoff, R.M., and B.T. Lamb
Opposing effects of membrane-anchored CX3CL1 on amyloid and tau pathologies via the p38 MAPK pathway
J. Neurosci., 34:12538-12546, 2014, PMCID: PMC4160782.
Jay, T.J., Miller, C.M., Cheng, P.J., Graham, L.C., Bemiller, S., Broihier, M.L., Xu, G., Margevicius, D., Karlo, J.C., Sousa, G.L., Cotleur, A.C., Butovsky, O., Bekris, L., Staugaitis, S.M., Leverenz, J.B., Pimplikar, S.W., Landreth, G.E., Howell, G.R., Ransohoff, R.M., and B.T. Lamb.
TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models
J. Exp. Med., 212:287-295, 2015, PMCID: PMC4354365.
Saber, M., Kokiko-Cochran, O.N., Puntambekar, S., Lathia, J., and B.T. Lamb.
TREM2 Deficiency alters acute macrophage distribution and improves recovery after TBI
J. Neurotrauma, In Press, 2016, PMID: 26976047.


Tuesday, January 31, 2017 - 12:30pm


Burke Medical Research Institute
785 Mamaroneck Avenue
White Plains, NY 10605
United States
Conference Room: 
Billings Building – Rosedale

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