Pharmacokinetic Differences of Grape Seed Procyanidins According to the Gavage Administration Between Normal Rats and Alzheimer's Disease Rats

2020 ◽  
Vol 17 (1) ◽  
pp. 119-128
Author(s):  
Xinhui Cheng ◽  
Jingying Zhang ◽  
Huiting Jing ◽  
Yu Qi ◽  
Tingxu Yan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mobile Phase ◽  
Plasma Concentrations ◽  
Research Work ◽  
Grape Seed ◽  
Plasma Samples ◽  
Natural Polyphenols ◽  
Shed Light ◽  
Over Time

Background: Grape Seed Procyanidins (GSP) refers to a type of natural polyphenols that have to roust antioxidant capacity. Studies have shed light on the fact that GSP significantly impacts the alleviation of Alzheimer's Disease (AD). Objective: This study aimed at investigating whether there exists a pharmacokinetics difference in GSP between normal and AD rats, a rapid UPLC-MS/MS methodology, for the detection of its content in plasma samples was put forward. We carried out an analysis of the plasma concentrations of procyanidin B2, procyanidin B3, catechin and epicatechin in normal and AD rats over time for determining the plasma concentration of GSP. Methods: We made use of 400 μL of methanol for the protein precipitation solvent in the plasma treatment. The chromatographic separation was carried out on a C18 column at a temperature of 20 °C. The mobile phase was a gradient of 0.1% formic acid in water and methanol within 15 min. Results: : In the current research work, the plasma concentrations of procyanidin B2, procyanidin B3, catechin and epicatechin in AD rats were significantly higher as compared with those in normal rats (P < 0.05) and the content of epicatechin constituted the highest as compared with catechin, procyanidin B2 and procyanidin B3 following the administration of GSP. Conclusion: We discovered the better absorptions of these analytes in the AD group as compared with that in the normal group, providing an analytical basis for treating the AD with procyanidins.

Impacts of Iron Metabolism Dysregulation on Alzheimer’s Disease

2021 ◽  
Vol 80 (4) ◽  
pp. 1439-1450
Author(s):  
Najla Jouini ◽  
Zakaria Saied ◽  
Samia Ben Sassi ◽  
Fatma Nebli ◽  
Taieb Messaoud ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant System ◽  
Plasma Concentrations ◽  
Normal Brain ◽  
Cognitively Normal ◽  
Iron Trafficking ◽  
Major Species ◽  
Normal Brain Function ◽  
Calcium Magnesium

Background: Iron plays an important role in maintaining cell survival, with normal iron trafficking known to be regulated by the ceruloplasmin-transferrin (Cp-Tf) antioxidant system. Disruption to this system is thought to be detrimental to normal brain function. Objective: To determine whether an imbalance of iron and the proteins involved in its metabolism (ceruloplasmin and transferrin) are linked to Alzheimer’s disease (AD) and to the expression of amyloid-beta (Aβ) peptide 1–42 (Aβ1–42), which is a major species of Aβ, and the most toxic. Methods: We evaluated the concentrations of iron, calcium, magnesium, and Aβ1–42 in the cerebrospinal fluid (CSF) of patients with AD and cognitively normal controls. Correlations between the components of the Cp-Tf antioxidant system in plasma were studied to determine the role of peripheral blood in the onset and/or development of AD. We used commercial ELISA immunoassays to measure Aβ1–42, immunoturbidimetry to quantify ceruloplasmin and transferrin, and colorimetry to quantify iron, calcium, and magnesium. Results: We found that the AD group had lower CSF concentrations of Aβ1–42 (p < 0.001) and calcium (p < 0.001), but a higher CSF concentration of iron (p < 0.001). Significantly lower plasma concentrations of ceruloplasmin (p = 0.003), transferrin (mean, p < 0.001), and iron (p < 0.001) were observed in the AD group than in cognitively normal adults. Moreover, we found a strong interdependence between most of these components. Conclusion: Iron dyshomeostasis has a crucial role in the onset of AD and/or its development. Correcting metal misdistribution is an appealing therapeutic strategy for AD.

[P3-237]: NEUROPEPTIDE YY PLASMA CONCENTRATIONS IN ALZHEIMER's DISEASE

2017 ◽  
Vol 13 (7S_Part_21) ◽  
pp. P1029-P1030
Author(s):  
Joseph L. Webb ◽  
Kylee Stitz ◽  
Anna Collazo-Martinez ◽  
Auriel A. Willette
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Concentrations

The Trajectory of Cerebrospinal Fluid Growth-Associated Protein 43 in the Alzheimer’s Disease Continuum: A Longitudinal Study

2021 ◽  
pp. 1-12
Author(s):  
Heng Zhang ◽  
Diyang Lyu ◽  
Jianping Jia ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Amyloid Β ◽  
Dementia Patients ◽  
Positron Emission ◽  
Potential Biomarker ◽  
Synaptic Degeneration ◽  
Over Time

Background: Synaptic degeneration has been suggested as an early pathological event that strongly correlates with severity of dementia in Alzheimer’s disease (AD). However, changes in longitudinal cerebrospinal fluid (CSF) growth-associated protein 43 (GAP-43) as a synaptic biomarker in the AD continuum remain unclear. Objective: To assess the trajectory of CSF GAP-43 with AD progression and its association with other AD hallmarks. Methods: CSF GAP-43 was analyzed in 788 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), including 246 cognitively normal (CN) individuals, 415 individuals with mild cognitive impairment (MCI), and 127 with AD dementia based on cognitive assessments. The associations between a multimodal classification scheme with amyloid-β (Aβ), tau, and neurodegeneration, and changes in CSF GAP-43 over time were also analyzed. Results: CSF GAP-43 levels were increased at baseline in MCI and dementia patients, and increased significantly over time in the preclinical (Aβ-positive CN), prodromal (Aβ-positive MCI), and dementia (Aβ-positive dementia) stages of AD. Higher levels of CSF GAP-43 were also associated with higher CSF phosphorylated tau (p-tau) and total tau (t-tau), cerebral amyloid deposition and hypometabolism on positron emission tomography, the hippocampus and middle temporal atrophy, and cognitive performance deterioration at baseline and follow-up. Furthermore, CSF GAP-43 may assist in effectively predicting the probability of dementia onset at 2- or 4-year follow-up. Conclusion: CSF GAP-43 can be used as a potential biomarker associated with synaptic degeneration in subjects with AD; it may also be useful for tracking the disease progression and for monitoring the effects of clinical trials.

scholarly journals Single-subject grey matter network trajectories over the disease course of autosomal dominant Alzheimer’s disease

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Lisa Vermunt ◽  
Ellen Dicks ◽  
Guoqiao Wang ◽  
Aylin Dincer ◽  
Shaney Flores ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Symptom Onset ◽  
Grey Matter ◽  
Autosomal Dominant ◽  
Single Subject ◽  
Mutation Carriers ◽  
Autosomal Dominant Alzheimer’S Disease ◽  
Network Properties ◽  
Over Time

Abstract Structural grey matter covariance networks provide an individual quantification of morphological patterns in the brain. The network integrity is disrupted in sporadic Alzheimer’s disease, and network properties show associations with the level of amyloid pathology and cognitive decline. Therefore, these network properties might be disease progression markers. However, it remains unclear when and how grey matter network integrity changes with disease progression. We investigated these questions in autosomal dominant Alzheimer’s disease mutation carriers, whose conserved age at dementia onset allows individual staging based upon their estimated years to symptom onset. From the Dominantly Inherited Alzheimer Network observational cohort, we selected T1-weighted MRI scans from 269 mutation carriers and 170 non-carriers (mean age 38 ± 15 years, mean estimated years to symptom onset −9 ± 11), of whom 237 had longitudinal scans with a mean follow-up of 3.0 years. Single-subject grey matter networks were extracted, and we calculated for each individual the network properties which describe the network topology, including the size, clustering, path length and small worldness. We determined at which time point mutation carriers and non-carriers diverged for global and regional grey matter network metrics, both cross-sectionally and for rate of change over time. Based on cross-sectional data, the earliest difference was observed in normalized path length, which was decreased for mutation carriers in the precuneus area at 13 years and on a global level 12 years before estimated symptom onset. Based on longitudinal data, we found the earliest difference between groups on a global level 6 years before symptom onset, with a greater rate of decline of network size for mutation carriers. We further compared grey matter network small worldness with established biomarkers for Alzheimer disease (i.e. amyloid accumulation, cortical thickness, brain metabolism and cognitive function). We found that greater amyloid accumulation at baseline was associated with faster decline of small worldness over time, and decline in grey matter network measures over time was accompanied by decline in brain metabolism, cortical thinning and cognitive decline. In summary, network measures decline in autosomal dominant Alzheimer’s disease, which is alike sporadic Alzheimer’s disease, and the properties show decline over time prior to estimated symptom onset. These data suggest that single-subject networks properties obtained from structural MRI scans form an additional non-invasive tool for understanding the substrate of cognitive decline and measuring progression from preclinical to severe clinical stages of Alzheimer’s disease.

Exploring Workload among Informal Caregivers of Persons with Dementia

2017 ◽  
Vol 61 (1) ◽  
pp. 1297-1297
Author(s):  
Rachel Zenker ◽  
Connor Pardell ◽  
Andrea Gilmore-Bykovskyi ◽  
Amy J. H. Kind ◽  
Nicole Werner
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Informal Caregiver ◽  
Informal Caregivers ◽  
Healthcare Delivery ◽  
Dynamic Environment ◽  
Informal Caregiving ◽  
Resource Scarcity ◽  
Structured Interviews ◽  
Over Time

Background: An estimated 5.3 million Americans are currently living with Alzheimer’s Disease or related dementias (Association 2015). Healthcare delivery for persons with Alzheimer’s Disease or related dementias (PwD), involves both the formal (e.g., physicians, social workers) and informal (e.g., family members, neighbors) work of healthcare. Informal caregiving for PwD totals approximately 18 billion hours of work per year and costs up to 217.7 billion dollars per year in caregiving costs, lost productivity and medical and institutional care (Association 2015). Informal caregivers must execute complex tasks in a dynamic environment often without the necessary information, resources, and training (Allegri, Sarasola et al. 2006, Gitlin, Kales et al. 2012). In addition, informal caregiving requires a physical, emotional, psychological, financial and temporal commitment from the informal caregiver. The confluence of these circumstances has the potential to influence the demands experienced by informal caregivers and the capacity to meet those demands. As informal caregivers increasingly take on healthcare tasks that were previously performed by trained professionals, it is important to understand how the workload experienced by informal caregivers and how it affects caregiving performance. Objective: To explore workload among informal caregivers of PwD to identify the influencers of capacity and demand and understand the interaction between capacity, demand, and caregiver burden. Method: We conducted in-depth semi-structured interviews (N=9) with informal caregivers of PwD to explore the workload among informal caregivers using qualitative thematic analysis. The interview questions related to the understanding of: 1) work performed by informal caregivers 2) strategies, tools, and resources used by informal caregivers 3) unmet needs related to caregiving work and 4) the environment in which the caregiving occurred. Results: We found three overarching themes related to caregiver workload: (1) informal caregiving demands surpass the capacity of any individual informal caregiver; (2) informal caregivers experienced dynamic workload that increased over time (i.e., as the disease progressed) forcing informal caregivers to seek assistance from other formal and informal caregiving resources; and (3) training, information, and resource scarcity is associated with informal caregiver work overload. Conclusions: Our results suggest that informal caregivers experience dynamic workload that increases over time, and that cannot be sustained by one person. Although informal caregivers were able to develop strategies to support workload, due to the progressive nature of the disease, specific strategies were not typically useful over time.

Mathematical Models to Shed Light on Amyloid-Beta and Tau Protein Dependent Pathologies in Alzheimer’s Disease

Neuroscience ◽  
2020 ◽  
Vol 424 ◽  
pp. 45-57
Author(s):  
Armin Vosoughi ◽  
Saeed Sadigh-Eteghad ◽  
Mohammad Ghorbani ◽  
Sedaghat Shahmorad ◽  
Mehdi Farhoudi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mathematical Models ◽  
Amyloid Beta ◽  
Tau Protein ◽  
Shed Light

scholarly journals Pre-Analytical and Within-Person Reproducibility of Nutritional Metabolomics over 2 Years in Elders at Risk for Dementia (P18-121-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gene Bowman ◽  
Natalia Gouskova ◽  
Hiroko Dodge ◽  
Juliana Donohue ◽  
Aline Bichsel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Measurement Errors ◽  
Brain Aging ◽  
Intraclass Correlation ◽  
Aging Research ◽  
Blood Samples ◽  
Time Points ◽  
Nutritional Metabolomics ◽  
Over Time

Abstract Objectives Nutritional metabolomics to objectively assess dietary intake in aging permit the opportunity to circumvent measurement errors that accompany subjective means of dietary assessment. At the same time, they may offer insights into mechanisms of action and metabolic disturbances that are actionable targets for modulation through diet in hopes of disease prevention and treatment. However, prior to more broad deployment the pre-analytical and temporal variation over time should be documented in order to design and interpret epidemiological studies properly. We quantified and examined 155 nutrient biomarkers and metabolites selected for their potential relevance to dementia. Methods Blood samples from three time points, spanning a 2-year period, were obtained from older adults participating in the NIA-Layton Oregon Alzheimer's Disease Center's Nutrition and Brain Aging Study (NBAS). Blood samples were batched randomly across three time points for quantification of blood amino acids, minerals, water and fat-soluble micronutrients, lipids, one carbon, and kynurenine pathway metabolites using a variety of methods including, tandem mass spectrometry. Pre-analytical coefficients of variation (CV) were calculated for all the biomarkers and intraclass correlation coefficients (ICC) were calculated to evaluate the within-person reproducibility in a subset of 137 participants. Results The mean baseline age of the analytic sample (n = 137) was 85.6 (± 8.3, 57 - 101 years), 70% are female, 21% carry the ApoEe4 allele and MMSE was 28.3 (± 1.78). The pre-analytical CVs ranged from 0.9% to 55.0% and the ICC ranged from 0 to 0.87 (25%-tile/median/75%-tile 0.41/0.54/0.66). Twenty four % had ICC < 0.40, 66% had ICC 0.40 −0.75 and 10% had ICC > 0.75. Conclusions The pre-analytical and within-person reproducibility of nutritional metabolomics in aging ranges widely. The majority can reliably estimate average concentrations over a 2 year period from a single time point and the biomarkers with ICC's above 0.40 can be used for correction of measurement error and those below 0.40 should consider multiple samples per subject and exploring the methodological and biological explanation for the variation over time. Funding Sources Nestle Institute of Health Sciences, Hinda and Arthur Marcus Institute for Aging Research, NIA-Layton Aging & Alzheimer's Disease Center (P30AGO8017).

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