scholarly journals Metal complexes designed to bind to amyloid-β for the diagnosis and treatment of Alzheimer's disease

2014 ◽  
Vol 43 (19) ◽  
pp. 6701-6715 ◽  
Author(s):  
David J. Hayne ◽  
SinChun Lim ◽  
Paul S. Donnelly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Complexes ◽  
Amyloid Β ◽  
Amyloid Imaging ◽  
Diagnosis And Treatment ◽  
Imaging Agents ◽  
Amyloid Formation ◽  
Amyloid Toxicity

The use radioactive copper and technetium complexes as amyloid imaging agents, the use of luminescent metal complexes as non-conventional probes of amyloid formation and the potential of metal complexes to be inhibitors of amyloid toxicity are discussed.

scholarly journals Distinct binding of amyloid imaging ligands to unique amyloid-β deposited in the presubiculum of Alzheimer's disease

2015 ◽  
Vol 135 (5) ◽  
pp. 859-866 ◽  
Author(s):  
Bin Ji ◽  
Chun-Jen Chen ◽  
Kazunori Bando ◽  
Hiroki Ashino ◽  
Hideaki Shiraishi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Imaging

scholarly journals Fibrillogenesis in Alzheimer's disease of amyloid β peptides and apolipoprotein E

1995 ◽  
Vol 306 (2) ◽  
pp. 599-604 ◽  
Author(s):  
E M Castano ◽  
F Prelli ◽  
T Wisniewski ◽  
A Golabek ◽  
R A Kumar ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Fibril Formation ◽  
Tau Proteins ◽  
Amyloid Formation

A central event in Alzheimer's disease is the conformational change from normally circulating soluble amyloid beta peptides (A beta) and tau proteins into amyloid fibrils, in the form of senile plaques and neurofibrillary tangles respectively. The apolipoprotein E (apoE) gene locus has recently been associated with late-onset Alzheimer's disease. It is not know whether apoE plays a direct role in the pathogenesis of the disease. In the present work we have investigated whether apoE can affect the known spontaneous in vitro formation of amyloid-like fibrils by synthetic A beta analogues using a thioflavine-T assay for fibril formation, electron microscopy and Congo Red staining. Our results show that, under the conditions used, apoE directly promotes amyloid fibril formation, increasing both the rate of fibrillogenesis and the total amount of amyloid formed. ApoE accelerated fibril formation of both wild-type A beta-(1-40) and A beta-(1-40A), an analogue created by the replacement of valine with alanine at residue 18, which alone produces few amyloid-like fibrils. However, apoE produced only a minimal effect on A beta-(1-40Q), found in the Dutch variant of Alzheimer's disease. When recombinant apoE isoforms were used, apoE4 was more efficient than apoE3 at enhancing amyloid formation. These in vitro observations support the hypothesis that apoE acts as a pathological chaperone, promoting the beta-pleated-sheet conformation of soluble A beta into amyloid fibres, and provide a possible explanation for the association of the apoE4 genetic isoform with Alzheimer's disease.

Development and Application of _-Amyloid Imaging Agents in Alzheimer’s Disease

The Dementias ◽  
2006 ◽  
pp. 279-301 ◽  
Author(s):  
William Klunk ◽  
Robert Nebes ◽  
Nicholas Tsopelas ◽  
Brian Lopresti ◽  
Julie Price ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Imaging ◽  
Imaging Agents

Amyloid toxicity in Alzheimer’s disease

2018 ◽  
Vol 29 (6) ◽  
pp. 613-627 ◽  
Author(s):  
Allison B. Reiss ◽  
Hirra A. Arain ◽  
Mark M. Stecker ◽  
Nicolle M. Siegart ◽  
Lora J. Kasselman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Pore Formation ◽  
Amyloid Β ◽  
Precursor Protein ◽  
Calcium Balance ◽  
Aβ Oligomers ◽  
Synaptic Loss ◽  
Amyloid Toxicity ◽  
Aβ Production

Abstract A major feature of Alzheimer’s disease (AD) pathology is the plaque composed of aggregated amyloid-β (Aβ) peptide. Although these plaques may have harmful properties, there is much evidence to implicate soluble oligomeric Aβ as the primary noxious form. Aβ oligomers can be generated both extracellularly and intracellularly. Aβ is toxic to neurons in a myriad of ways. It can cause pore formation resulting in the leakage of ions, disruption of cellular calcium balance, and loss of membrane potential. It can promote apoptosis, cause synaptic loss, and disrupt the cytoskeleton. Current treatments for AD are limited and palliative. Much research and effort is being devoted to reducing Aβ production as an approach to slowing or preventing the development of AD. Aβ formation results from the amyloidogenic cleavage of human amyloid precursor protein (APP). Reconfiguring this process to disfavor amyloid generation might be possible through the reduction of APP or inhibition of enzymes that convert the precursor protein to amyloid.

scholarly journals Amyloid-β adopts a conserved, partially folded structure upon binding to zwitterionic lipid bilayers prior to amyloid formation

2016 ◽  
Vol 52 (5) ◽  
pp. 882-885 ◽  
Author(s):  
Kyle J. Korshavn ◽  
Anirban Bhunia ◽  
Mi Hee Lim ◽  
Ayyalusamy Ramamoorthy
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lipid Bilayer ◽  
Lipid Bilayers ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Amyloid Formation ◽  
Folded Structure

Aggregation at the neuronal cell membrane's lipid bilayer surface is implicated in amyloid-β (Aβ) toxicity associated with Alzheimer's disease; however, structural and mechanistic insights into the process remain scarce.

[IM-10]: The application of amyloid-imaging to the diagnosis and treatment of Alzheimer's disease

2005 ◽  
Vol 1 ◽  
pp. S5-S5
Author(s):  
William E. Klunk ◽  
Julie C. Price ◽  
Steven T. DeKosky ◽  
Chester A. Mathis
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Imaging ◽  
Diagnosis And Treatment

scholarly journals Modulation of amyloid-β aggregation by metal complexes with a dual binding mode and their delivery across the blood-brain barrier using focused ultrasound

2021 ◽  
Author(s):  
Ramon Vilar ◽  
Tiffany G Chan ◽  
Carmen Ruehl ◽  
Sophie Morse ◽  
Michelle Simon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Metal Complexes ◽  
Blood Brain Barrier ◽  
Focused Ultrasound ◽  
Amyloid Β ◽  
Binding Mode ◽  
Brain Barrier ◽  
Amyloid Β Peptide ◽  
Blood Brain

One of the key hallmarks of Alzheimer’s disease is the aggregation of the amyloid-β peptide to form fibrils. Consequently, there has been great interest in studying molecules that can disrupt...

scholarly journals Nutrient signaling pathways regulate amyloid clearance and synaptic loss in Alzheimer’s disease

2020 ◽  
Author(s):  
Mrityunjoy Mondal ◽  
Jitin Bali ◽  
Makis Tzioras ◽  
Rosa C. Paolicelli ◽  
Ali Jawaid ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Pathological State ◽  
Amyloid Formation ◽  
Synaptic Loss ◽  
Synapse Loss ◽  
Human Neurons ◽  
Nutrient Signaling

SummaryExtra-cellular accumulation of Amyloid-β (Aβ) plaques is causatively associated with Alzheimer’s disease (AD). However, mechanisms that mediate the pre-pathological state of amyloid plaque formation remain elusive. Here, using paired RNAi and kinase inhibitor screens, we discovered that AKT-mediated insulin/nutrient signaling suppresses lysosomal clearance of Aβ and promotes amyloid formation. This mechanism is cell-autonomous and functions in multiple systems, including iPSC-derived human neurons and in vivo. Nutrient signaling regulates amyloid formation via distinct lysosomal functional mechanisms, while enhanced amino acid signaling promotes amyloid formation by transcriptionally suppressing lysosome biogenesis, and high intracellular cholesterol levels suppress lysosomal clearance of amyloid by increasing the number of non-functional lysosomes. The nutrient signaling pathway, present in both neurons and microglia, regulates lysosomal clearance of amyloid and microglia mediated synapse loss, both in vitro and in vivo. Clinically, older hyperlipidemic patients showed less synapse loss through microglia and performed better in cognitive tests. Thus, our results reveal a bi-partite cellular quality control system regulated by the insulinnutrient signaling that in neurons regulates Aβ peptide clearance and in microglia regulates synaptic loss, both processes causally associated with AD. Our results also caution against reducing amyloid through such processes as this might also result in synapse loss.

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