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Alzheimer's disease (AD) is an incurable neurodegenerative disease that leads to the progressive and irreversible loss of mental functions. The amyloid beta (Aβ) peptide involved in the disease is responsible for the production of damaging reactive oxygen species (ROS) when bound to Cu ions. A therapeutic approach that consists of removing Cu ions from Aβ to alter this deleterious interaction is currently being developed. In this context, we report the ability of five different 12-membered thiaazacyclen ligands to capture Cu from Aβ and to redox silence it. We propose that the presence of a sole sulfur atom in the ligand increases the rate of Cu capture and removal from Aβ, while the kinetic aspect of the chelation was an issue encountered with the 4N parent ligand. The best ligand for removing Cu from Aβ and inhibiting the associated ROS production is the 1-thia-4,7,10-triazacyclododecane [3N1S]. Indeed the replacement of more N by S atoms makes the corresponding Cu complexes easier to reduce and thus able to produce ROS on their own. In addition, the ligand with three sulfur atoms has a weaker affinity for Cu II than Aβ, and is thus unable to remove Cu from CuAβ., (© 2023 Wiley-VCH GmbH.)

Two Keggin polyoxometalates were used as new copper ligands to counteract the effects of Cu II (Amyloid-β) interaction. Their ability to remove Cu II from Cu II (Amyloid-β), to stop Cu II (Amyloid-β) induced formation of reactive oxygen species and to restore apo-like self-assembly of Cu II (Amyloid-β) was shown.

Introduction: Understanding of Alzheimer disease (AD) is fundamental for early diagnosis and to reduce caregiver burden. The objective of this study is to evaluate the degree of understanding of AD among informal caregivers and different segments of the general population through the Alzheimer's Disease Knowledge Scale (ADKS)., Patients and Methods: We assessed the knowledge of caregivers in different follow-up periods (less than one year, between 1 and 5 years, and over 5 years since diagnosis) and individuals from the general population. ADKS scores were grouped into different items: life impact, risk factors, symptoms, diagnosis, treatment, disease progression, and caregiving., Results: A total of 419 people (215 caregivers and 204 individuals from the general population) were included in the study. No significant differences were found between groups for overall ADKS score (19.1 vs 18.8, P = .9). There is a scarce knowledge of disease risk factors (49.3%) or the care needed (51.2%), while symptoms (78.6%) and course of the disease (77.2%) were the best understood aspects. Older caregiver age was correlated with worse ADKS scores overall and for life impact, symptoms, treatment, and disease progression (P < .05). Time since diagnosis improved caregivers' knowledge of AD symptoms (P = .00) and diagnosis (P = .05)., Conclusion: Assessing the degree of understanding of AD is essential to the development of health education strategies both in the general population and among caregivers., (Copyright © 2018 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: The aim of this study was to investigate the usefulness of Alzheimer's disease Cerebrospinal Fluid (CSF) biomarkers in predicting the progression to dementia in patients with Mild Cognitive Impairment (MCI)., Methods: One hundred and thirteen patients were consecutively recruited from April 2012 to April 2014. Measurement of CSF biomarkers (amyloid-β42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau)) and a neuropsychological evaluation were performed for all patients. We categorized patients with MCI as A+A- and N+N- based on the presence/absence of amyloid pathology and neurodegeneration, respectively., Results: Of 72 patients with MCI, 26 (36%) progressed to dementia. These patients had lower CSF Aβ42 levels and higher p-tau and t-tau levels at baseline. The proportion that progressed to dementia was 14.3% (2/14), 36.8% (7/19), 66.7% (4/6) and 75% (12/16) in the A-N-, A+N-, A-N+ (SNAP), and A+N+ patients, respectively (p < 0.05). There were significant differences in the probability of progression from amnestic MCI (aMCI) to AD between the A+N+ and A-N- patients (OR = 8.1, 95% CI 1.5-42.3, p = 0.001) but not between SNAP (OR = 7.3, 95% CI 0.9-61, p = 0.02) or A+N- (OR = 2.1, 95% CI 0.4 to 10.4, p = 0.15) patients compared to the A-N- subgroup. None of the biomarker profiles of the subgroups predicted the time until the progression to AD., Conclusion: The use of CSF AD biomarkers in clinical practice improves the certainty of diagnosis and prognosis of patients, especially in patients in the prodromal phase or in patients with atypical presentations., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Copper(I) coordinating ligands in the Alzheimer's disease context have remained unexplored, despite the biological relevance of this redox state of the copper ion. Here, we show that the PTA ligand can remove copper from Aβ, prevent reactive oxygen species production and oligomer formation, two deleterious events in the disease's etiology.