scholarly journals Plasma Biomarkers of Alzheimer’s Disease in African Americans

2021 ◽  
Vol 79 (1) ◽  
pp. 323-334
Author(s):  
Kaancan Deniz ◽  
Charlotte C.G. Ho ◽  
Kimberly G. Malphrus ◽  
Joseph S. Reddy ◽  
Thuy Nguyen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
African Americans ◽  
Plasma Proteins ◽  
Plasma Concentrations ◽  
Disease Status ◽  
Lower Plasma ◽  
Plasma Biomarkers ◽  
Pairwise Correlations ◽  
Inflammatory Proteins

Background/Objective: The aim of this study was to determine if plasma concentrations of 5 surrogate markers of Alzheimer’s disease (AD) pathology and neuroinflammation are associated with disease status in African Americans. Methods: We evaluated 321 African Americans (159 AD, 162 controls) from the Florida Consortium for African-American Alzheimer’s Disease Studies (FCA3DS). Five plasma proteins reflecting AD neuropathology or inflammation (Aβ42, tau, IL6, IL10, TNFα) were tested for associations with AD, age, sex, APOE and MAPT genotypes, and for pairwise correlations. Results: Plasma tau levels were higher in AD when adjusted for biological and technical covariates. APOE ɛ4 was associated with lower plasma Aβ42 and tau levels. Older age was associated with higher plasma Aβ42, tau, and TNFα. Females had lower IL10 levels. Inflammatory proteins had strong pairwise correlations amongst themselves and with Aβ42. Conclusion: We identified effects of demographic and genetic variants on five potential plasma biomarkers in African Americans. Plasma inflammatory biomarkers and Aβ42 may reflect correlated pathologies and elevated plasma tau may be a biomarker of AD in this population.

scholarly journals Plasma Biomarkers: Potent Screeners of Alzheimer’s Disease

2019 ◽  
Vol 34 (5) ◽  
pp. 290-301 ◽  
Author(s):  
Muhammad Naveed ◽  
Shamsa Mubeen ◽  
Abeer Khan ◽  
Sehrish Ibrahim ◽  
Bisma Meer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Proteins ◽  
Great Accuracy ◽  
Vital Role ◽  
Brain Cell ◽  
Plasma Biomarkers ◽  
Factors Associated ◽  
Specificity And Sensitivity ◽  
Complex Chronic Disease

Alzheimer’s disease (AD), a neurological disorder, is as a complex chronic disease of brain cell death that usher to cognitive decline and loss of memory. Its prevalence differs according to risk factors associated with it and necropsy performs vital role in its definite diagnosis. The stages of AD vary from preclinical to severe that proceeds to death of patient with no availability of treatment. Biomarker may be a biochemical change that can be recognized by different emerging technologies such as proteomics and metabolomics. Plasma biomarkers, 5-protein classifiers, are readily being used for the diagnosis of AD and can also predict its progression with a great accuracy, specificity, and sensitivity. In this review, upregulation or downregulation of few plasma proteins in patients with AD has also been discussed, when juxtaposed with control, and thus serves as potent biomarker in the diagnosis of AD.

scholarly journals Blood metabolite markers of cognitive performance and brain function in aging

2015 ◽  
Vol 36 (7) ◽  
pp. 1212-1223 ◽  
Author(s):  
Brittany N Simpson ◽  
Min Kim ◽  
Yi-Fang Chuang ◽  
Lori Beason-Held ◽  
Melissa Kitner-Triolo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Function ◽  
Memory Performance ◽  
Verbal Learning ◽  
Plasma Concentrations ◽  
Brain Regions ◽  
Older Individuals ◽  
Lower Plasma ◽  
Positron Emission

We recently showed that Alzheimer's disease patients have lower plasma concentrations of the phosphatidylcholines (PC16:0/20:5; PC16:0/22:6; and PC18:0/22:6) relative to healthy controls. We now extend these findings by examining associations between plasma concentrations of these PCs with cognition and brain function (measured by regional resting state cerebral blood flow; rCBF) in non-demented older individuals. Within the Baltimore Longitudinal Study of Aging neuroimaging substudy, participants underwent cognitive assessments and brain 15O-water positron emission tomography. Plasma phosphatidylcholines concentrations (PC16:0/20:5, PC16:0/22:6, and PC18:0/22:6), cognition (California Verbal Learning Test (CVLT), Trail Making Test A&B, the Mini-Mental State Examination, Benton Visual Retention, Card Rotation, and Fluencies—Category and Letter), and rCBF were assessed. Lower plasma phosphatidylcholine concentrations were associated with lower baseline memory performance (CVLT long delay recall task—PC16:0/20:5: −2.17–1.39−0.60 p = 0.001 (β with 95% confidence interval subscripts)) and lower rCBF in several brain regions including those associated with memory performance and higher order cognitive processes. Our findings suggest that lower plasma concentrations of PC16:0/20:5, PC16:0/22:6, and PC18:0/22:6 are associated with poorer memory performance as well as widespread decreases in brain function during aging. Dysregulation of peripheral phosphatidylcholine metabolism may therefore be a common feature of both Alzheimer's disease and age-associated differences in cognition.

scholarly journals Multiplex proteomics identifies novel CSF and plasma biomarkers of early Alzheimer’s disease

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Christopher D. Whelan ◽  
Niklas Mattsson ◽  
Michael W. Nagle ◽  
Swetha Vijayaraghavan ◽  
Craig Hyde ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Proteins ◽  
Proteomic Profiling ◽  
Plasma Biomarkers ◽  
Csf Proteins ◽  
Normal Individuals ◽  
Angiogenic Proteins ◽  
Prodromal Ad ◽  
Early Alzheimer’S Disease

Abstract To date, the development of disease-modifying therapies for Alzheimer’s disease (AD) has largely focused on the removal of amyloid beta Aβ fragments from the CNS. Proteomic profiling of patient fluids may help identify novel therapeutic targets and biomarkers associated with AD pathology. Here, we applied the Olink™ ProSeek immunoassay to measure 270 CSF and plasma proteins across 415 Aβ- negative cognitively normal individuals (Aβ- CN), 142 Aβ-positive CN (Aβ+ CN), 50 Aβ- mild cognitive impairment (MCI) patients, 75 Aβ+ MCI patients, and 161 Aβ+ AD patients from the Swedish BioFINDER study. A validation cohort included 59 Aβ- CN, 23 Aβ- + CN, 44 Aβ- MCI and 53 Aβ+ MCI. To compare protein concentrations in patients versus controls, we applied multiple linear regressions adjusting for age, gender, medications, smoking and mean subject-level protein concentration, and corrected findings for false discovery rate (FDR, q < 0.05). We identified, and replicated, altered levels of ten CSF proteins in Aβ+ individuals, including CHIT1, SMOC2, MMP-10, LDLR, CD200, EIF4EBP1, ALCAM, RGMB, tPA and STAMBP (− 0.14 < d < 1.16; q < 0.05). We also identified and replicated alterations of six plasma proteins in Aβ+ individuals OSM, MMP-9, HAGH, CD200, AXIN1, and uPA (− 0.77 < d < 1.28; q < 0.05). Multiple analytes associated with cognitive performance and cortical thickness (q < 0.05). Plasma biomarkers could distinguish AD dementia (AUC = 0.94, 95% CI = 0.87–0.98) and prodromal AD (AUC = 0.78, 95% CI = 0.68–0.87) from CN. These findings reemphasize the contributions of immune markers, phospholipids, angiogenic proteins and other biomarkers downstream of, and potentially orthogonal to, Aβ- and tau in AD, and identify candidate biomarkers for earlier detection of neurodegeneration.

scholarly journals Discovery of plasma protein biomarkers related to Alzheimer’s disease, sex and APOE genotype

2020 ◽  
Author(s):  
Scott B. Laffoon ◽  
James D. Doecke ◽  
Anne M. Roberts ◽  
Jennifer A. Vance ◽  
Benjamin D. Reeves ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Proteins ◽  
Fluorescent Protein ◽  
Plasma Concentrations ◽  
Apoe Genotype ◽  
Protein Detection ◽  
Complement Factor ◽  
Differential Analysis ◽  
Two Dimensional Gel Electrophoresis

AbstractThe Australian Imaging and Biomarker Lifestyle (AIBL) study of aging is designed to aid the discovery of biomarkers. The current study aimed to discover differentially expressed plasma proteins that could yield a blood-based screening tool for Alzheimer’s disease. To search for biomarkers and elucidate mechanisms of AD, we immuno-depleted the most abundant plasma proteins and pre-fractionated the remaining proteins by HPLC, prior to two-dimensional gel electrophoresis. The relative levels of approximately 3,400 protein species resolved on the 2D gels were compared using in-gel differential analysis with spectrally resolved fluorescent protein detection dyes (Zdyes™). Here we report on analysis of pooled plasma samples from an initial screen of a sex-matched cohort of 72 probable AD patients and 72 healthy controls from the baseline time point of AIBL. We report significant changes in variants of apolipoprotein E, haptoglobin, α1 anti-trypsin, inter-α trypsin inhibitor, histidine-rich glycoprotein, and a protein of unknown identity. α1 anti-trypsin and α1 anti-chymotrypsin demonstrated plasma concentrations that were dependent on APOE ε4 allele dose. Our analysis also identified an association with the level of Vitamin D binding protein fragments and complement factor I with sex. We then conducted a validation study on individual samples using a targeted LC-MS/MS assay. This study indicates that a peripheral protein signature has potential to aid in the characterization of AD. We also found significant associations of protein levels with APOE genotype, indicating that differences in genotype influence the circulating abundances of proteins other than ApoE.

Association Between the APOE ɛ2/ɛ4 Genotype and Alzheimer’s Disease and Mild Cognitive Impairment Among African Americans

2021 ◽  
pp. 1-6
Author(s):  
Dianxu Ren ◽  
Oscar L. Lopez ◽  
Jennifer H. Lingler ◽  
Yvette Conley
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
African Americans ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Increased Risk ◽  
Similar Risk

We examined the association between APOE ɛ2/ɛ4 with incident Alzheimer’s disease (AD) and mild cognitive impairment (MCI) among African Americans using the national dataset from the National Alzheimer’s Coordinating Center (NACC) from 2005 to September 2019. Compared to ɛ3/ɛ3 carriers, ɛ2/ɛ4 carriers exhibited a similar risk of incident AD (adjusted hazard ratio [aHR] = 0.85, 95% CI [0.39, 1.84]) among the AD cohort and similar risk of incident MCI (aHR = 0.88, 95% CI [0.51, 1.50]) among the MCI cohort. Our findings suggest that, unlike the increased risk of AD and MCI in non-Latino whites, APOE ɛ2/ɛ4 genotype is not associated with the incidence of AD and MCI among African Americans.

scholarly journals CSF metabolites associate with CSF tau and improve prediction of Alzheimer's disease status

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Ruocheng Dong ◽  
Burcu F. Darst ◽  
Yuetiva Deming ◽  
Yue Ma ◽  
Qiongshi Lu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Status

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.

O3-02-05: Proteomic identification of plasma biomarkers for hippocampal atrophy in Alzheimer's disease

2008 ◽  
Vol 4 ◽  
pp. T161-T161
Author(s):  
Madhav Thambisetty ◽  
Andrew Simmons ◽  
Abdul Hye ◽  
Darragh O'Brien ◽  
James Campbell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hippocampal Atrophy ◽  
Plasma Biomarkers ◽  
Proteomic Identification

Hippocampal and amygdalar morphological abnormalities in Alzheimer’s disease based on three Chinese MRI datasets

2021 ◽  
Vol 18 ◽  
Author(s):  
Yuanyuan Wei ◽  
Nianwei Huang ◽  
Yong Liu ◽  
Xi Zhang ◽  
Silun Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Shape Analysis ◽  
Early Stage ◽  
Disease Status ◽  
Brain Structures ◽  
Statistical Shape Analysis ◽  
Social Significance ◽  
Statistical Shape ◽  
Shape Characteristics

Background: Early detection of Alzheimer’s disease (AD) and its early stage, the mild cognitive impairment (MCI), has important scientific, clinical and social significance. Magnetic resonance imaging (MRI) based statistical shape analysis provides an opportunity to detect regional structural abnormalities of brain structures caused by AD and MCI. Objective: In this work, we aimed to employ a well-established statistical shape analysis pipeline, in the framework of large deformation diffeomorphic metric mapping, to identify and quantify the regional shape abnormalities of the bilateral hippocampus and amygdala at different prodromal stages of AD, using three Chinese MRI datasets collected from different domestic hospitals. Methods: We analyzed the region-specific shape abnormalities at different stages of the neuropathology of AD by comparing the localized shape characteristics of the bilateral hippocampi and amygdalas between healthy controls and two disease groups (MCI and AD). In addition to group comparison analyses, we also investigated the association between the shape characteristics and the Mini Mental State Examination (MMSE) of each structure of interest in the disease group (MCI and AD combined) as well as the discriminative power of different morphometric biomarkers. Results: We found the strongest disease pathology (regional atrophy) at the subiculum and CA1 subregions of the hippocampus and the basolateral, basomedial as well as centromedial subregions of the amygdala. Furthermore, the shape characteristics of the hippocampal and amygdalar subregions exhibiting the strongest AD related atrophy were found to have the most significant positive associations with the MMSE. Employing the shape deformation marker of the hippocampus or the amygdala for automated MCI or AD detection yielded a significant accuracy boost over the corresponding volume measurement. Conclusion: Our results suggested that the amygdalar and hippocampal morphometrics, especially those of shape morphometrics, can be used as auxiliary indicators for monitoring the disease status of an AD patient.

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