Charles Glabe, Ph.D.

Headshot photo

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
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.

2013
$100,000
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.

2011
$100,000
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.

2009
$250,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

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