Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by the accumulation of abnormal tau proteins within neurons and amyloid plaques in the brain parenchyma, which leads to progressive loss of neurons in the brain. While the detailed mechanism of the pathogenesis of AD is still unknown, evidence suggests that mitochondrial dysfunction likely plays a fundamental role in the pathogenesis of this disease. Due to the relevance of mitochondrial alterations in AD, recent works have suggested the therapeutic potential of mitochondrial-targeted lithium. Lithium has been shown to possess neuroprotective and neurotrophic properties that could also be related to the upregulation of mitochondrial function. In the current work, we perform a comprehensive investigation of the significance of mitochondrial dysfunction in AD and pharmacological treatment with lithium as imperative in this pathology, through a brief review of the major findings on the effects of lithium as a therapeutic approach targeting mitochondria in the context of AD.
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http://dx.doi.org/10.1016/j.neulet.2021.136078 | DOI Listing |
Liver Transpl
October 2024
Department of General Surgery, Division of Transplantation, Medical University of Vienna, Vienna, Austria.
Hypothermic oxygenated machine perfusion (HOPE) preconditions liver grafts before transplantation. While beneficial effects on patient outcomes were demonstrated, biomarkers for viability assessment during HOPE are scarce and lack validation. This study aims to validate the predictive potential of perfusate flavin mononucleotide (FMN) during HOPE to enable the implementation of FMN-based assessment into clinical routine and to identify safe organ acceptance thresholds.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA.
Background: The mitochondrial cascade hypothesis suggests that mitochondrial dysfunction plays an important role in the pathogenesis of Alzheimer's disease dementia. Recent data have shown that mitochondrial DNA copy number (mtDNAcn) in human blood is associated with dementia risk and cognitive function, but which specific cognitive measures or domains are associated with mitochondrial dysfunction and whether this relationship is affected by health deterioration such as physical frailty or mitochondrial somatic mutations is not clear.
Methods: We measured mtDNAcn and heteroplasmies using fastMitoCalc and MitoCaller, respectively, from UK Biobank Whole Genome Sequencing (WGS) data at study entry (2006-2010).
Alzheimers Dement
December 2024
University of California, Los Angeles Integrative Biology and Physiology (IBP), Los Angeles, CA, USA.
Background: APOE is in linkage disequilibrium with the length of poly-T repeats at the rs10524523 ('523) locus of the TOMM40 gene. APOE-ε3 is associated with short (S) and (VL) variants of '523 in white and Black individuals. In white individuals, APOE-ε4 is associated with the long (L) '523 variant, but is associated with '523-S, '523-L, and '523-VL variants in Black individuals.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Huntington Medical Research Institutes, Pasadena, CA, USA.
Background: Dicarboxylic acids (DCAs) are critically important for intermediate metabolism. Since mitochondrial dysfunction and energy dysregulation are associated with AD pathology, we hypothesize that fluctuations in plasma DCAs would accompany AD pathology.
Method: In an ongoing brain-aging study, we recruited older adults (>65 years) classified as cognitively healthy (CH) after neuropsychological testing.
Background: Two main risk factors of Alzheimer's disease (AD) are aging and APOE-ε4. However, some individuals remain cognitively normal despite having these risk factors. They are considered "cognitively resilient".
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