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    Increased susceptibility to oxidative death of lymphocytes from Alzheimer patients correlates with dementia severity
    (2014-03)
    Ponce, Daniela
    ;
    Salech, Felipe
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    Sanmartin, Carol
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    Silva, Mónica
    ;
    Xiong, Chengjie
      3
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    1278 Feasibility of 48-h Ambulatory BP Assessment in Latinos with Dementia
    (Oxford University Press (OUP), 2025-05)
    Mili Jimenez Gallardo
    ;
    Andrea Castillo Suárez
    ;
    Peng Li
    ;
    Ramon C Hermida
    ;
    Michael Smolensky
    Abstract Introduction Ambulatory blood pressure (BP) monitoring encapsulates 24-h BP patterns across the sleep-wake cycle and provides a comprehensive assessment of BP regulation with certain features, such as sleep-time dipping, that can better predict health outcomes than traditional office BP measurements. However, 24-h BP patterns remain understudied in Latino populations, especially older adults. This pilot study investigated the feasibility of continuously ambulatory BP monitoring blood pressure with portable devices in Latinos with dementia. Methods Eight participants (4 with Alzheimer’s disease, 1 with Frontotemporal dementia, 3 controls; age range 45.8-80.3 years) from the ReDLat cohort (Multi-Partner Consortium to Expand Dementia Research in Latin America) were enrolled for a 48-h ambulatory BP assessment with hourly measurements using a portable arm-cuff device. Participants also answered six questions to evaluate: (1) device adaption, (2) measurement frequency tolerability, (3) study duration acceptability, (4) perceived value of the assessment, (5) willingness to perform the assessment again, and (6) likelihood of recommending the assessment to others. Results The study yielded high-quality recordings with minimal missing BP measurements (range: 0%-14.1%; mean: 8.9%). Device adaptation improved over time, with 75% (6/8) reporting better tolerance on the second day and 25% (2/8) reporting consistently good tolerance across both days. All participants reported that hourly BP measurement was tolerable, and majority (7/8, 87.5%) found 48-h monitoring acceptable. Seven participants (87.5%) believed that the assessment was valuable, were willing to participate again, and likely recommend to others the assessment. Conclusion Our findings demonstrate that 48-hour ambulatory BP monitoring is feasible and well-tolerated among older Latino adults with mild to moderate dementia in Latin American settings. Further feasibility testing should be performed in large samples and other populations, including individuals at later stages of dementia and in different countries.
      4
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    The exposome of brain aging across 34 countries
    (Springer Science and Business Media LLC, 2026-04-03)
    Agustina Legaz
    ;
    Sebastian Moguilner
    ;
    Pablo Barttfeld
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    Jhosmary Cuadros Castro
    ;
    Dante Sebastián Galván Rial
    Scopus© Citations 7  1
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    Comprehensive Analysis of Genetic Contributions to Alzheimer’s Disease and Frontotemporal Dementia in Admixed Latin American Populations
    (Wiley, 2024-12)
    Juliana Acosta‐Uribe
    ;
    Stefanie Danielle Pina Escudero
    ;
    J. Nicholas Cochran
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    Jared W Taylor
    ;
    Caroline Warly Solsberg
    <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Most research initiatives have emerged from high‐income countries (HIC), leaving a gap in understanding the disease’s genetic basis in diverse populations like those in Latin American countries (LAC). ReDLat tackles this gap, focusing on LAC’s unique genetics and socioeconomic factors to identify specific Alzheimer’s Disease (AD) and Frontotemporal Dementia (FTD) risk factors in Mexico, Colombia, Peru, Chile, Argentina, and Brazil.</jats:p></jats:sec><jats:sec><jats:title>Method</jats:title><jats:p>We employed a comprehensive genetic analysis approach, integrating Whole Genome Sequencing (WGS), Exome Sequencing, and SNP arrays to understand the cohort’s unique genetic architecture. We conducted ancestry analysis and searched for disease‐causing variants with mendelian inheritance, genome‐wide association studies (GWAS), rare variant enrichment, and evaluation of Polygenic Risk Scores (PRS).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>We recruited and genotyped an initial cohort of 1046 participants with AD, 423 with FTD, and 855 healthy controls (HC) between 2020 and 2023. Analysis is ongoing, and we expect to sequence ∼600 additional samples in the coming months. Ancestry analysis revealed tri‐continental admixture, except for Brazil, which showed an additional Asian component (Figure 1). Top candidate gene rare variant enrichment associations (SKAT p &lt; 0.05) were <jats:italic>TREM2</jats:italic> for FTD and <jats:italic>ABCA7</jats:italic> and <jats:italic>ABCA1</jats:italic> for AD. GWAS identified a robust association with the <jats:italic>APOE</jats:italic> locus on chromosome 19 in AD vs. HC.. We tested an AD PRS developed in European populations by Bellenguez et al (2020). on our cohort using 83 single‐nucleotide polymorphisms.. The PRS modestly distinguishes between all patients and HC (p = 2.4 × 10^‐12), AD vs. HC (p = 2.2 × 10^‐12), and even FTD vs. HC (p = 4.3 × 10^‐5), albeit with modest separation between groups, as expected for its application in a genetically admixed population.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Our findings represent a pivotal step in understanding the genetic landscape of AD and FTD in admixed populations. They underscore the importance of including diverse populations in genetic research, paving the way for future studies. These findings have the potential to inform more personalized approaches to the diagnosis and treatment of neurodegenerative diseases in diverse global populations, as well as identify novel targets for therapeutic development.</jats:p></jats:sec>
      3
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      2Scopus© Citations 8
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    Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease
    (2021)
    Laura Gómez-Virgilio
    ;
    Alejandro Luarte
    ;
    Daniela P. Ponce
    ;
    Bárbara A. Bruna
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    <jats:p>Among all the proposed pathogenic mechanisms to understand the etiology of Alzheimer’s disease (AD), increased oxidative stress seems to be a robust and early disease feature where many of those hypotheses converge. However, despite the significant lines of evidence accumulated, an effective diagnosis and treatment of AD are not yet available. This limitation might be partially explained by the use of cellular and animal models that recapitulate partial aspects of the disease and do not account for the particular biology of patients. As such, cultures of patient-derived cells of peripheral origin may provide a convenient solution for this problem. Peripheral cells of neuronal lineage such as olfactory neuronal precursors (ONPs) can be easily cultured through non-invasive isolation, reproducing AD-related oxidative stress. Interestingly, the autofluorescence of key metabolic cofactors such as reduced nicotinamide adenine dinucleotide (NADH) can be highly correlated with the oxidative state and antioxidant capacity of cells in a non-destructive and label-free manner. In particular, imaging NADH through fluorescence lifetime imaging microscopy (FLIM) has greatly improved the sensitivity in detecting oxidative shifts with minimal intervention to cell physiology. Here, we discuss the translational potential of analyzing patient-derived ONPs non-invasively isolated through NADH FLIM to reveal AD-related oxidative stress. We believe this approach may potentially accelerate the discovery of effective antioxidant therapies and contribute to early diagnosis and personalized monitoring of this devastating disease.</jats:p>
      7Scopus© Citations 9