scholarly journals Cross-interactions between the Alzheimer disease amyloid-β peptide and other amyloid proteins.A FURTHER ASPECT OF THE AMYLOID CASCADE HYPOTHESIS.

2017 ◽  
Vol 292 (5) ◽  
pp. 2046-2046 ◽  
Author(s):  
Jinghui Luo ◽  
Sebastian K. T. S. Wärmländer ◽  
Astrid Gräslund ◽  
Jan Pieter Abrahams
Keyword(s):  
Alzheimer Disease ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Amyloid Cascade

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

Challenging the Amyloid Cascade Hypothesis: Senile Plaques and Amyloid-β as Protective Adaptations to Alzheimer Disease

2004 ◽  
Vol 1019 (1) ◽  
pp. 1-4 ◽  
Author(s):  
HYOUNG-GON LEE ◽  
GEMMA CASADESUS ◽  
XIONGWEI ZHU ◽  
ATSUSHI TAKEDA ◽  
GEORGE PERRY ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Amyloid Cascade Hypothesis ◽  
Amyloid Cascade

Kinetic fingerprints differentiate anti-Aβ therapies

2019 ◽  
Author(s):  
Sara Linse ◽  
Tom Scheidt ◽  
Katja Bernfur ◽  
Michele Vendruscolo ◽  
Christopher M. Dobson ◽  
...  
Keyword(s):  
Self Assembly ◽  
Clinical Stage ◽  
Amyloid Β ◽  
Therapeutic Agents ◽  
Mechanisms Of Action ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
The Past ◽  
Amyloid Cascade ◽  
Oligomeric Forms

The amyloid cascade hypothesis, according to which the self-assembly of amyloid-β peptide (Aβ) is a causative process in Alzheimer’s disease, has driven many therapeutic efforts for the past 20 years. Failures of clinical trials investigating Aβ-targeted therapies have been interpreted as evidence against this hypothesis, irrespective of the characteristics and mechanisms of action of the therapeutic agents, which are highly challenging to assess. We bring together kinetic analysis with quantitative binding measurements to address the mechanisms of action of four clinical stage anti-Aβ antibodies, aducanumab, gantenerumab, bapineuzumab and solanezumab. We reveal and quantify the striking differences of these antibodies on the aggregation kinetics and on the production of oligomeric aggregates, and link these effects to the affinity and stoichiometry of each antibody for monomeric and fibrillar forms of Aβ. Our results uncover that, uniquely amongst these four antibodies, aducanumab dramatically reduces the flux of oligomeric forms of Aβ.

scholarly journals In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

2010 ◽  
Vol 48 (1) ◽  
pp. 136-144 ◽  
Author(s):  
D. Allan Butterfield ◽  
Veronica Galvan ◽  
Miranda Bader Lange ◽  
Huidong Tang ◽  
Renã A. Sowell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Methionine 35

Making and Remaking Alzheimer Disease

2013 ◽  
Author(s):  
Margaret Lock
Keyword(s):  
Alzheimer Disease ◽  
Normal Aging ◽  
Research Paradigm ◽  
Amyloid Cascade Hypothesis ◽  
The Past ◽  
Localization Theory ◽  
Initial Identification ◽  
Aging Populations ◽  
Amyloid Cascade

This chapter focuses on the “discovery” of Alzheimer disease (AD) and a somewhat condensed genealogy of its history to the present time. Emphasis is given to the virtual disappearance of AD for over four decades after its initial identification, followed by its rediscovery in the late 1960s in association with government and medical recognition of aging populations and their impending burden on society. The chapter also discusses the consolidation of what has been the dominant research paradigm in AD research for the past four decades-the amyloid cascade hypothesis, grounded in localization theory. Throughout the study, difficulties in attempting to unravel the entanglement of “normal” aging from dementia, evident from Alois Alzheimer's time, are pointed out.

scholarly journals Identification of Novel γ-Secretase-associated Proteins in Detergent-resistant Membranes from Brain

2012 ◽  
Vol 287 (15) ◽  
pp. 11991-12005 ◽  
Author(s):  
Ji-Yeun Hur ◽  
Yasuhiro Teranishi ◽  
Takahiro Kihara ◽  
Natsuko Goto Yamamoto ◽  
Mitsuhiro Inoue ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Affinity Purification ◽  
Amyloid Β ◽  
Anion Channel ◽  
Amyloid Β Peptide ◽  
Voltage Dependent Anion Channel ◽  
App Processing ◽  
Associated Proteins ◽  
Detergent Resistant Membranes ◽  
Aβ Production

In Alzheimer disease, oligomeric amyloid β-peptide (Aβ) species lead to synapse loss and neuronal death. γ-Secretase, the transmembrane protease complex that mediates the final catalytic step that liberates Aβ from its precursor protein (APP), has a multitude of substrates, and therapeutics aimed at reducing Aβ production should ideally be specific for APP cleavage. It has been shown that APP can be processed in lipid rafts, and γ-secretase-associated proteins can affect Aβ production. Here, we use a biotinylated inhibitor for affinity purification of γ-secretase and associated proteins and mass spectrometry for identification of the purified proteins, and we identify novel γ-secretase-associated proteins in detergent-resistant membranes from brain. Furthermore, we show by small interfering RNA-mediated knockdown of gene expression that a subset of the γ-secretase-associated proteins, in particular voltage-dependent anion channel 1 (VDAC1) and contactin-associated protein 1 (CNTNAP1), reduced Aβ production (Aβ40 and Aβ42) by around 70%, whereas knockdown of presenilin 1, one of the essential γ-secretase complex components, reduced Aβ production by 50%. Importantly, these proteins had a less pronounced effect on Notch processing. We conclude that VDAC1 and CNTNAP1 associate with γ-secretase in detergent-resistant membranes and affect APP processing and suggest that molecules that interfere with this interaction could be of therapeutic use for Alzheimer disease.

scholarly journals Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease

10.1038/78682 ◽  
2000 ◽  
Vol 6 (8) ◽  
pp. 916-919 ◽  
Author(s):  
Frédérique Bard ◽  
Catherine Cannon ◽  
Robin Barbour ◽  
Rae-Lyn Burke ◽  
Dora Games ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Alzheimer Disease ◽  
Mouse Model ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
The Central Nervous System
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