Oxidative pathomechanisms play an important role in neurodegenerative diseases like Alzheimer's disease (AD). It has been shown that lipid peroxidation in cerebrospinal fluid (CSF) and plasma is increased in AD. To assess the role of oxidative stress in Creutzfeldt-Jakob disease (CJD), we investigated the oxidizability of lipids, the lipid composition and the levels of the antioxidants ascorbate and alpha-tocopherol in CSF and plasma of 15 CJD patients and 12 neurologically healthy controls. CSF and plasma lipid peroxidation was increased in CJD patients and polyunsaturated fatty acids were reduced in CSF of these patients. Ascorbate levels were lower in CSF and plasma of CJD patients, while alpha-tocopherol was found to be decreased in CSF but not in plasma. These results support the hypothesis that oxidative mechanisms are involved in the pathogenesis of CJD and provide a rationale for the use of antioxidants in the therapy of this disease.
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http://dx.doi.org/10.1006/nbdi.2002.0496 | DOI Listing |
Alzheimers Dement
December 2024
GSK R&D, Stevenage, Hertfordshire, United Kingdom.
Background: Genetic variants in GRN, the gene encoding progranulin, are causal for or are associated with the risk of multiple neurodegenerative diseases. Modulating progranulin has been considered as a therapeutic strategy for neurodegenerative diseases including Frontotemporal Dementia (FTD) and Alzheimer's Disease (AD). Here, we integrated genetics with proteomic data to determine the causal human evidence for the therapeutic benefit of modulating progranulin in AD.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) composed of tau aggregates. Research in animal models has generated hypotheses on the underlying mechanisms of the interaction between Aβ and tau pathology. In support of this interaction, results from clinical trials have shown that treatment with anti-Aβ monoclonal antibodies (mAbs) affects tau pathology.
View Article and Find Full Text PDFBackground: CT1812 is an experimental therapeutic sigma-2 receptor modulator in development for Alzheimer's disease (AD) and dementia with Lewy bodies. CT1812 reduces the affinity of Aβ oligomers to bind to neurons and exert synaptotoxic effects. This phase 2, multi-center, international, randomized, double-blind, placebo-controlled trial assessed safety, tolerability and effects of CT1812 on cognitive function in individuals with AD.
View Article and Find Full Text PDFBackground: Impaired Aβ clearance plays a key role in the common, late-onset AD. Anti-Aβ immunotherapies are controversial, in part because of high rates of serious side effects including edema, microhemorrhages, and siderosis, highlighting the importance of the development of alternative Aβ clearance strategy. Here, we introduce a bioinspired nanoparticle named MG-PE3 crossing the human blood-brain barrier (BBB) and clearing Aβ with no adverse effect.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
National Institute on Aging, NIH, Baltimore, MD, USA.
Background: Epidemiological studies report an elevated risk of neurodegenerative disorders, particularly Parkinson's disease (PD), in patients with type 2 diabetes mellitus (T2DM) that is mitigated in those prescribed incretin mimetics or dipeptidyl peptidase 4 inhibitors (DPP-4Is). Incretin mimetic repurposing appears promising in human PD and Alzheimer's disease (AD) clinical trials. DPP-4Is are yet to be evaluated in PD or AD human studies.
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