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Browsing by Subject "Amyloid beta"
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Item Alzheimer's disease and inflammatory biomarkers positively correlate in plasma in the UK‐ADRC cohort(Wiley, 2024) Foley, Kate E.; Winder, Zachary; Sudduth, Tiffany L.; Martin, Barbara J.; Nelson, Peter T.; Jicha, Gregory A.; Harp, Jordan P.; Weekman, Erica M.; Wilcock, Donna M.; Neurology, School of MedicineIntroduction: Protein-based plasma assays provide hope for improving accessibility and specificity of molecular diagnostics to diagnose dementia. Methods: Plasma was obtained from participants (N = 837) in our community-based University of Kentucky Alzheimer's Disease Research Center cohort. We evaluated six Alzheimer's disease (AD)- and neurodegeneration-related (Aβ40, Aβ42, Aβ42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNF𝛼, IL6, IL8, IL10, and GFAP) using the SIMOA-based protein assay platform. Statistics were performed to assess correlations. Results: Our large cohort reflects previous plasma biomarker findings. Relationships between biomarkers to understand AD-inflammatory biomarker correlations showed significant associations between AD and inflammatory biomarkers suggesting peripheral inflammatory interactions with increasing AD pathology. Biomarker associations parsed out by clinical diagnosis (normal, MCI, and dementia) reveal changes in strength of the correlations across the cognitive continuum. Discussion: Unique AD-inflammatory biomarker correlations in a community-based cohort reveal a new avenue for utilizing plasma-based biomarkers in the assessment of AD and related dementias. Highlights: Large community cohorts studying sex, age, and APOE genotype effects on biomarkers are few. It is unknown how biomarker-biomarker associations vary through aging and dementia. Six AD (Aβ40, Aβ42, Aβ42/40, p-tau181, total tau, and NfLight) and five inflammatory biomarkers (TNFα, IL6, IL8, IL10, and GFAP) were used to examine associations between biomarkers. Plasma biomarkers suggesting increasing cerebral AD pathology corresponded to increases in peripheral inflammatory markers, both pro-inflammatory and anti-inflammatory. Strength of correlations, between pairs of classic AD and inflammatory plasma biomarker, changes throughout cognitive progression to dementia.Item Contribution of Alzheimer's biomarkers and risk factors to cognitive impairment and decline across the Alzheimer's disease continuum(Wiley, 2022) Tosun, Duygu; Demir, Zeynep; Veitch, Dallas P.; Weintraub, Daniel; Aisen, Paul; Jack, Clifford R., Jr.; Jagust, William J.; Petersen, Ronald C.; Saykin, Andrew J.; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of MedicineIntroduction: Amyloid beta (Aβ), tau, and neurodegeneration jointly with the Alzheimer's disease (AD) risk factors affect the severity of clinical symptoms and disease progression. Methods: Within 248 Aβ-positive elderly with and without cognitive impairment and dementia, partial least squares structural equation pathway modeling was used to assess the direct and indirect effects of imaging biomarkers (global Aβ-positron emission tomography [PET] uptake, regional tau-PET uptake, and regional magnetic resonance imaging-based atrophy) and risk-factors (age, sex, education, apolipoprotein E [APOE], and white-matter lesions) on cross-sectional cognitive impairment and longitudinal cognitive decline. Results: Sixteen percent of variance in cross-sectional cognitive impairment was accounted for by Aβ, 46% to 47% by tau, and 25% to 29% by atrophy, although 53% to 58% of total variance in cognitive impairment was explained by incorporating mediated and direct effects of AD risk factors. The Aβ-tau-atrophy pathway accounted for 50% to 56% of variance in longitudinal cognitive decline while Aβ, tau, and atrophy independently explained 16%, 46% to 47%, and 25% to 29% of the variance, respectively. Discussion: These findings emphasize that treatments that remove Aβ and completely stop downstream effects on tau and neurodegeneration would only be partially effective in slowing of cognitive decline or reversing cognitive impairment.Item Correction to: Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases(BMC, 2022-09-09) Perez, Felipe P.; Bandeira, Joseph P.; Perez Chumbiauca, Cristina N.; Lahiri, Debomoy K.; Morisaki, Jorge; Rizkalla, Maher; Medicine, School of MedicineCorrection to: Journal of Biomedical Science (2022) 29:39 https://doi.org/10.1186/s12929-022-00825-yItem Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment(Frontiers Media, 2023-04-18) Kim, Hang-Rai; Jung, Sang-Hyuk; Kim, Beomsu; Kim, Jaeho; Jang, Hyemin; Kim, Jun Pyo; Kim, So Yeon; Na, Duk L.; Kim, Hee Jin; Nho, Kwangsik; Won, Hong-Hee; Seo, Sang Won; Alzheimer’s Disease Neuroimaging Initiative; Radiology and Imaging Sciences, School of MedicineBackground: The genetic basis of amyloid β (Aβ) deposition in subcortical vascular cognitive impairment (SVCI) is still unknown. Here, we investigated genetic variants involved in Aβ deposition in patients with SVCI. Methods: We recruited a total of 110 patients with SVCI and 424 patients with Alzheimer's disease-related cognitive impairment (ADCI), who underwent Aβ positron emission tomography and genetic testing. Using candidate AD-associated single nucleotide polymorphisms (SNPs) that were previously identified, we investigated Aβ-associated SNPs that were shared or distinct between patients with SVCI and those with ADCI. Replication analyses were performed using the Alzheimer's Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Rush Memory and Aging Project cohorts (ROS/MAP). Results: We identified a novel SNP, rs4732728, which showed distinct associations with Aβ positivity in patients with SVCI (P interaction = 1.49 × 10-5); rs4732728 was associated with increased Aβ positivity in SVCI but decreased Aβ positivity in ADCI. This pattern was also observed in ADNI and ROS/MAP cohorts. Prediction performance for Aβ positivity in patients with SVCI increased (area under the receiver operating characteristic curve = 0.780; 95% confidence interval = 0.757-0.803) when rs4732728 was included. Cis-expression quantitative trait loci analysis demonstrated that rs4732728 was associated with EPHX2 expression in the brain (normalized effect size = -0.182, P = 0.005). Conclusion: The novel genetic variants associated with EPHX2 showed a distinct effect on Aβ deposition between SVCI and ADCI. This finding may provide a potential pre-screening marker for Aβ positivity and a candidate therapeutic target for SVCI.Item Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases(BMC, 2022-06-13) Perez, Felipe P.; Bandeira, Joseph P.; Perez Chumbiauca, Cristina N.; Lahiri, Debomoy K.; Morisaki, Jorge; Rizkalla, Maher; Medicine, School of MedicineWe provide a multidimensional sequence of events that describe the electromagnetic field (EMF) stimulation and biological system interaction. We describe this process from the quantum to the molecular, cellular, and organismal levels. We hypothesized that the sequence of events of these interactions starts with the oscillatory effect of the repeated electromagnetic stimulation (REMFS). These oscillations affect the interfacial water of an RNA causing changes at the quantum and molecular levels that release protons by quantum tunneling. Then protonation of RNA produces conformational changes that allow it to bind and activate Heat Shock Transcription Factor 1 (HSF1). Activated HSF1 binds to the DNA expressing chaperones that help regulate autophagy and degradation of abnormal proteins. This action helps to prevent and treat diseases such as Alzheimer's and Parkinson's disease (PD) by increasing clearance of pathologic proteins. This framework is based on multiple mathematical models, computer simulations, biophysical experiments, and cellular and animal studies. Results of the literature review and our research point towards the capacity of REMFS to manipulate various networks altered in aging (Reale et al. PloS one 9, e104973, 2014), including delay of cellular senescence (Perez et al. 2008, Exp Gerontol 43, 307-316) and reduction in levels of amyloid-β peptides (Aβ) (Perez et al. 2021, Sci Rep 11, 621). Results of these experiments using REMFS at low frequencies can be applied to the treatment of patients with age-related diseases. The use of EMF as a non-invasive therapeutic modality for Alzheimer's disease, specifically, holds promise. It is also necessary to consider the complicated and interconnected genetic and epigenetic effects of the REMFS-biological system's interaction while avoiding any possible adverse effects.