Modulating Amyloid-β Levels by Immunotherapy: A Potential Therapeutic

Cynthia A. Lemere, Timothy J. Seabrook, Melitza Iglesias, Chica Mori, Jodi F. Leverone and Edward T. Spooner

Alzheimer's disease (AD) is the most common form of dementia and afflicts ~15-20 million people worldwide. Currently, there is no effective cure. Research efforts over the past decade have demonstrated that amyloid-beta protein (Aβ), a small peptide generated from its large precurso...

Potential Role of Endogenous and Exogenous Aβ Binding Molecules in Aβ Clearance and Metabolism

Donald B. DeMattos, Kelly R. Bales, Steven M. Paul and David M. Holtzman

Alzheimer's disease (AD) is the leading cause of dementia in the elderly and there are currently no effective therapies for either the prevention or treatment of this disease. The last decade of AD research has been very informative in that major advances have occurred in the understandi...

Transport-Clearance Hypothesis for Alzheimer's Disease and Potential Therapeutic

Berislav V. Zlokovic and Blas Frangione

Alzheimer's disease (AD) is the major cause of dementia and the most common form of human amyloidosis. AD affects an astoundingly large number of people and is common with advancing age. The brains of Alzheimer's patients are typically riddled with insoluble "plaques" which con...

Amyloid β-Protein in Low-Density Membrane Domains

Maho Morishima-Kawashima and Yasuo lhara

Membrane microdomains, which have just been emerging thanks to recent technological progress, may have significant roles in normal cell functions such as adhesion, signaling, and trafficking. We found that a significant amount of amyloid β-protein (Aβ) is located to the cholest...

Aβ Metabolism in Cholesterol Enriched Membrane Microdomains

Todd E. Golde and M. Paul Murphy

Aggregation and accumulation of Aβ is a pathological hallmark of the Alzheimer's disease (AD) brain. Studies on cerebrospinal fluid (CSF) from living patients and postmortem control brain tissue show the normal level of Aβ in the brain to be in the low nM range. Biophysical stu...

Aβ Degradation by Endothelin-Converting Enzymes

Elizabeth A. Eckman and Christopher B. Eckman

The abnormal accumulation of β-amyloidloid (Aβ) in the brain is an early and invariant feature of Alzheimer's disease and is believed to play a pivotal role in the etiology and pathogenesis of the disease. The concentration of Aβ is regulated by multiple enzymatic activiti...

Proteolytic Degradation of Aβ by Neprilysin and Other Peptidases

Takaomi C. Saido and Hiroyuki Nakahara

Amyloid β peptide (Aβ), the pathogenic agent of Alzheimer's disease (AD), is a physiological metabolite in the brain. We focused our attention and effort on elucidation of the unresolved aspect of Aβ metabolism, proteolytic degradation. Among a number of Aβ-degrading ...

Functional Roles of APP Secretases

Cleavage of APP by α-, β and γ-secretases strikingly resembles regulated intramembrane proteolysis (RIP), which is normally employed to generate signaltransducing fragments from transmembrane proteins. Protein 'RIPping' is initiated by signals like ligand binding causin...

γ -Secretase and Presenilin

Michael S. Wolfe

Because production and deposition of the amyloid-β peptide (Aβ) is intimately linked to the pathogenesis of Alzheimer's disease (AD), the proteases responsible for excising Aβ from the amyloid-β precursor protein (APP), β- and γ-secretases, are considered i...

APP α -Secretase, a Novel Target for Alzheimer Drug Therapy

Shoichi Ishiura, Masashi Asai, Chinatsu Hattori, Nika Hotoda, Beata Szabo, Noboru Sasagawa and Sei-ichi Tanuma

The neurodegeneration in Alzheimer's disease (AD) may be caused by deposition of amyloid β peptide (Aβ) in plaques in brain tissue (amyloid hypothesis). Mechanisms of Aβ production in the brain have been the subject of considerable interest. Several factors regulate processing o...

β - Secretase: Progress and Open Questions

Martin Citron

Finding inhibitors of Aβ42 generation is a major goal of Alzheimer's disease drug development. Two target protease activities, β-and γ-secretases, were operationally defined more than 10 years ago, but progress in this area has been slow because the actual enzymes were no...

Overview - Aβ Metabolism: From Alzheimer

Takaomi C. Saido

Readers and authors of this book alike are the allies of scientists and scientists-to-be in the fight against one of our most common and mightiest enemies, Alzheimer's disease (AD), which deprives individuals of their basic human dignity after decades of (generally) respectful lives with...