Moir, Robert

MoirRobert Moir, PhD
Assistant Professor in Neurology, Genetics and Aging Research Unit
Massachusetts General Hospital and Harvard Medical School, Charlestown, MA

“Aβ, Alzheimer’s, and Lyme Disease”

Dr Moir complete his Ph.D at the University of Melbourne in Australia under the mentorship of Prof Colin Masters, one of the founders of the modern field of Alzheimer’s disease (AD) research. Dr Moir immigrated to the US in 1994 and joined the Genetics and Aging Research Unit (GARU) shortly after the group’s formation. Dr Moir now heads his own research lab within GARU and has been a faculty member of Harvard Medical School and Massachusetts General Hospital since 1998. Dr Moir’s research focus is the interaction of biomolecules involved in AD pathology.

Dr Moir’s research focuses on the biochemical and cellular mechanisms of neurodegeneration in Alzheimer’s disease (AD) and aging. His work has uncovered new therapeutic targets aimed at preventing the accumulation of beta-amyloid (Aβ), the primary neurotoxic agent in AD. Moir was the first to identify the low-density lipoprotein receptor protein (LRP) as the mediator of an important early step in Aβ production in the brain. Today, LRP-mediated Aβ clearance pathways are increasingly recognized as major targets for therapeutic intervention. His work revealed the importance of metals in the pathological aggregation of Aβ, leading directly to the investigation of the copper and zinc chelator clioquinol in clinical trials for AD. Dr Moir has also helped establish Aβ’s role in the formation of eye lens cataracts in AD patients, which could lead to better diagnosis of the disease.

His studies on the immune response to amyloid have revealed potential abnormalities in protective Aβ-reactive autoantibodies in AD patients. Therapeutic strategies for AD that are based on this find have lead to the development of artificial antibodies currently in third phase clinical trials. Dr Moir’s most recent studies have identified the normal biological function of Aβ. Aβ is a member of the antimicrobial peptide family of innate immune proteins. Antimicrobial peptides are natural antibiotic that acts as part of the innate immune system to trap and kill pathogens invading the brain. This novel discovery suggests AD may be an inappropriate response to a real or falsely perceived infection in the brain. This finding may also shed light on the pathological mechanisms associated with other major amyloid-associated diseases, including diabetes and arteriosclerosis.

Conference Lecture Summary

Recent confirmation of a protective antimicrobial role for the amyloid-β (Aβ) protein of Alzheimer’s disease (AD) has fueled debate on the role of infection in AD etiology. Aβ appears to belong to the antimicrobial peptide (AMP) family of immune proteins. AMPs are natural antibiotics and immunomodulators that act as the foot soldiers of innate immunity. Infection in transgenic animal models of AD leads to protective entrapment of microbes within β-amyloid plaques. Deposition of β-amyloid is a histological hallmark of AD. Here we discuss pathways leading to β-amyloid mediated microbial entrapment and the implications of Aβ’s emerging innate immune role for an AD/Lyme disease link.