Charles Glabe, Ph.D.

Professor, Molecular Biology and Biochemistry, School of Biological Sciences, University of California at Irvine

Dr. Glabe's research program is focused on amyloid structure and aggregation, in particular beta-amyloid, which is the key pathogenic hallmark of Alzheimer's disease. Dr. Glabe made the seminal discovery that protein components of amyloid share a common structure that is recognized by a conformation-specific antibody. This discovery indicates that amyloids likely share a common primary mechanism of pathogenesis in disease.


Funded Research

Project Description Researchers Funding
Identification of a Protective Human Immune Response for Alzheimer’s Disease

Immunotherapy is a leading strategy for preventing cognitive decline in Alzheimer’s disease. Administering a monoclonal antibody to beta amyloid aggregates in patients with mild cognitive impairment showed some positive impact on cognitive decline over the course of a year in a clinical trial, but effective dosages are tied to negative side effects.

Long Abetas, Intraneuronal Amyloid and an Alternative Amyloid Hypothesis of Alzheimer’s Disease

The goal of this proposal is to test a new paradigm for the causative mechanisms of Alzheimer’s disease (AD): The accumulation of amyloid aggregates inside neurons leading to their degeneration and initiating plaque formation. The hypothesis we will test is the inverse or mirror image of the commonly held view of the amyloid hypothesis of AD, which proposes that soluble Abeta is secreted from neurons, aggregates in the extracellular space and causes neuronal dysfunction from the outside.

Characterization of the pathological significance of a novel type of vascular amyloid

The amyloid Aß peptide is deposited in at least two distinct locations in AD brain:  Parenchymal plaques and vascular amyloid deposits in the wall of arterioles, where it is associated with vascular smooth muscle cell degeneration and stroke (Congophilic amyloid angiopathy, CAA).  While CAA is commonly found in AD brain, some human mutations within the Aß domain of the amyloid precursor protein (APP) cause CAA and stroke, rather than AD indicating that these diseases can occur independently.

Cellular and Animal Models of Amyloid Pathology in Early Alzheimer's Disease

The goal of this project is to evaluate the pathological significance of a new type of Abeta deposits in the brain (at the onset of Alzheimer’s disease) in order to develop a novel mechanism for amyloid pathogenesis to help convince the FDA to approve and support early clinical trials.

Potential for Host Cytotoxicity from Microbially-derived Abeta Oligomers

Alzheimer’s disease (AD) is the most common form of dementia in the elderly afflicting over 20 million people worldwide. Two decades of findings from cell biology, genetic, neuropathological, biochemical and animal studies overwhelmingly point to the β-amyloid peptide (Aβ) as the key protein in the disease’s pathology (see review by Hardy and Selkoe, 20001). Aβ appears to be a soluble component of normal brain. However, in AD brain the peptide accumulates as β-amyloid, an insoluble semi-crystalline deposit that is the hallmark of the disease pathology.

Oligomer Collaborative Projects

A collaboration of members of the Research Consortium, a member of the Cure Alzheimer’s Fund Science Advisory Board and non-Cure Alzheimer’s Fund-affiliated researchers hypothesizes that an abnormal increase in levels of synaptic Abeta and, particularly, Abeta oligomers may lead to synaptic dysfunction, cognitive decline and eventually dementia. This highly innovative collaborative project will address how Abeta oligomers are formed and which types detrimentally impact synaptic dysfunction and neuronal survival in the brain.

2006 to 2008


Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.
Jean-Vianney Haure-Mirande, Mickael Audrain, Tomas Fanutza, Soong Ho Kim, William L. Klein, Charles Glabe, Ben Readhead, Joel T. Dudley, Robert D. Blitzer, Minghui Wang, Bin Zhang, Eric E. Schadt, Sam Gandy, Michelle E. Ehrlich, Deficiency of TYROBP, an adapter protein for TREM2 and CR3 receptors, is neuroprotective in a mouse model of early Alzheimer's pathology, Acta Neuropathologica, 134(5), Nov 2017, 769-788
Elysse M. Knight, PhD, Soong Ho Kim, PhD, Jessica C. Kottwitz, BS, Asa Hatami, PhD, Ricardo Albay, BS, Akinobu Suzuki, PhD, Alex Lublin, PhD, Cristina M. Alberini, PhD, William L. Klein, PhD, Paul Szabo, PhD, Norman R. Relkin, MD, PhD, Michelle Ehrlich, MD, Charles G. Glabe, PhD, Sam Gandy, MD, PhD and John W. Steele, PhD, Effective anti-Alzheimer Aβ therapy involves depletion of specific Aβ oligomer subtypes, Neurol Neuroimmunol Neuroinflamm, 3(3), May 2016
J W Steele, M L Lachenmayer, S Ju, A Stock, J Liken, S H Kim, L M Delgado, I E Alfaro, S Bernales, G Verdile, P Bharadwaj, V Gupta, R Barr, A Friss, G Dolios, R Wang, D Ringe, P Fraser, D Westaway, P H St George-Hyslop, P Szabo, N R Relkin, J D Buxbaum, C G Glabe, A A Protter, R N Martins, M E Ehrlich, G A Petsko, Z Yue and S Gandy, Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model, Mol Psychiatry, 18(8), Aug 2013, 889-897
Arai H, Glabe C, Luecke H, Crystal structure of a conformation-dependent rabbit IgG Fab specific for amyloid prefibrillar oligomers, Biochim Biophys Acta, 1820(12), Dec 2012, 1908-14
Nussbaum, JM; Schilling, S; Cynis, H; Silva, A; Swanson, E; Wangsanut, T; Tayler, K; Wiltgen, B; Hatami, A; Ronicke, R; Reymann, K; Hutter-Paier, B; Alexandru, A; Jagla, W; Graubner, S; Glabe, CG; Demuth, HU; Bloom, GS, Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β, Nature, 485, May 2, 2012, 651-655
Gandy S, Simon AJ, Steele JW, Lublin AL, Lah JJ, Walker LC, Levey AI, Krafft GA, Levy E, Checler F, Glabe C, Bilker WB, Abel T, Schmeidler J, Ehrlich ME, Days to criterion as an indicator of toxicity associated with human Alzheimer amyloid-β oligomers, Annals of Neurology, Volume 68, Issue 2, August 2010
Kayed, R., Pensalfini, A., Margol, L., Sokolov, Y., Sarsoza, F., Head, E., Hall, J., and Glabe, C, Annular protofibrils are a structurally and functionally distinct type of amyloid oligomer, J Biol Chem, 284, February 13, 2009, 4230-4237
Glabe, CG, Structural classification of toxic amyloid oligomers, J Biol Chem, 283, October 31, 2008, 29639-29643