The Role of TREM2, a Key Immune Regulating Protein, in Alzheimer’s Disease

Bruce Lamb, PhD
Cleveland Clinic Lerner Research Institute (Cleveland, OH)
Year Awarded:
2015
Grant Duration:
July 1, 2015 to June 30, 2019
Disease:
Alzheimer's Disease
Award Amount:
$250,000
Grant Reference ID:
A2015296S
Award Type:
Standard
Award Region:
US Midwestern
Bruce Lamb, PhD

The Role of TREM2 in AD Tauopathy

Summary

We are working to find new drug targets in the brain and to understand the biology of the newly identified immune molecule, triggering receptor expressed on myeloid cells 2, or TREM2, and its role in the Alzheimer’s disease (AD) tau pathology. There are a variety of different cell types in the brain, some of which are normally present, and some of which are recruited into the brain when it is diseased. We want to better understand the interactions of these cells and identify specific and unique therapeutic targets.

Details

The TREM2 genetic variant has been shown to confer increased risk of developing late-onset AD (LOAD) and to elevated risk for other neurodegenerative diseases, including  frontotemporal dementia, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).  However, virtually nothing is known regarding the role of TREM2 in tauopathy. Based upon recently published preliminary studies we hypothesize that TREM2 ablation will result in reduced inflammation within the brain, along with improved pathological outcomes, in a mouse model that develops protein aggregates (tau pathology) similar to those observed in human AD. In Aim 1, we will explore the role of TREM2 in modulating pathological outcomes in the hTau mouse model of AD tau pathology, focusing on effects on inflammation, neurodegeneration, and behavior. In Aim 2, we will characterize the impact of TREM2 deficiency on gene expression patterns within immune cells of the brain. There are a variety of different immune cell types in the brain, some of which are normally present, and some of which that are recruited into the brain when it is diseased. We want to better understand the interactions of these cells and identify specific and unique therapeutic targets that will impact Alzheimer's disease brain pathologies. 

About the Researcher

Bruce Lamb, PhD is staff scientist in the Department of Neurosciences in the Lerner Research Institute at the Cleveland Clinic.  Dr. Lamb received his bachelor’s degree from Swarthmore College and his PhD from the University of Pennsylvania, prior to a post-doctoral fellowship at Johns Hopkins University. In 1996, Dr. Lamb was recruited to Case Western Reserve University, where he rose from assistant to associate professor and finally moved to the Cleveland Clinic in 2005. Dr. Lamb’s laboratory works on the basic science of AD, with a focus on: 1) genetic modifiers identified from both mouse and human studies, 2) microglia and neuronal-microglial communication in the development and progression of AD pathologies; and 3) traumatic brain injury as an environmental modifier for the development of AD pathologies. In addition, Dr. Lamb is actively involved in advocacy for increased research funding for the disease. Dr. Lamb has received numerous awards and honors, including the Jennifer B. Langston Award from the Cleveland Chapter of the Alzheimer’s Association and the National Civic Award and Zaven Khachaturian Lifetime Achievement Award form the National Alzheimer’s Association. He is a Fellow in the American Association for the Advancement of Science and a member of the Medical and Scientific Advisory Council of the National Alzheimer’s Association.


"Over the past several years, Dr. Lamb has emerged as a national leader in advocacy to build awareness regarding Alzheimer’s disease (AD); promote the important role of AD research; and support efforts to develop a comprehensive national plan for combating the disease in the coming years. In 2010, Dr. Lamb conceived, organized and executed the Alzheimer’s Breakthrough Ride (ABR), a relay-style bike ride involving over 55 Alzheimer’s researchers who rode a total of 4500 miles across the entirety of the United States. The goal of the ride was to garner petition signatures in support of pending Alzheimer’s legislation, including the National Alzheimer’s Project Act (NAPA), which initiated a national plan for AD, as well as to raise public awareness regarding the disease.

By the time the ABR reached Washington, DC, over 110,000 signatures from individuals all across the United States were delivered to Capitol Hill. In addition, at the end of the ride, researchers met with more than 50 members of Congress and Dr. Lamb attended the first-ever White House briefing on the challenge of AD in the United States. In late 2010, NAPA was unanimously approved by both houses of Congress and was signed into law by President Barack Obama on January 4, 2011. The NAPA Advisory Council was formed in August 2011, and an initial national plan on AD created in early 2012. Dr. Lamb is also an active member of Leaders Engaged in Alzheimer’s Disease (LEAD), an open coalition of Alzheimer’s research, care and advocacy communities which provides feedback and recommendations to the NAPA Advisory Council."

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