Browsing by Subject "Biomarkers"
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Item Acute Regression in Down Syndrome(MDPI, 2021-08-23) Handen, Benjamin; Clare, Isabel; Laymon, Charles; Petersen, Melissa E.; Zaman, Shahid; O'Bryant, Sid E.; Minhas, Davneet; Tudorascu, Dana; Brown, Stephanie; Christian, BradleyAcute regression has been reported in some individuals with Down syndrome (DS), typically occurring between the teenage years and mid to late 20s. Characterized by sudden, and often unexplained, reductions in language skills, functional living skills and reduced psychomotor activity, some individuals have been incorrectly diagnosed with Alzheimer's disease (AD).|This paper compares five individuals with DS who previously experienced acute regression with a matched group of 15 unaffected individuals with DS using a set of AD biomarkers.|While the sample was too small to conduct statistical analyses, findings suggest there are possible meaningful differences between the groups on proteomics biomarkers (e.g., NfL, total tau). Hippocampal, caudate and putamen volumes were slightly larger in the regression group, the opposite of what was hypothesized. A slightly lower amyloid load was found on the PET scans for the regression group, but no differences were noted on tau PET.|Some proteomics biomarker findings suggest that individuals with DS who experience acute regression may be at increased risk for AD at an earlier age in comparison to unaffected adults with DS. However, due to the age of the group (mean 38 years), it may be too early to observe meaningful group differences on image-based biomarkers.Item Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry(Informa UK Limited, trading as Taylor & Francis Group, 2017-10-27) Lewczuk, Piotr; Riederer, Peter; O'Bryant, Sid E.; Verbeek, Marcel M.; Dubois, Bruno; Visser, Pieter Jelle; Jellinger, Kurt A.; Engelborghs, Sebastiaan; Ramirez, Alfredo; Parnetti, Lucilla; Jack, Clifford R.; Teunissen, Charlotte E.; Hampel, Harald; Lleó, Alberto; Jessen, Frank; Glodzik, Lidia; de Leon, Mony J.; Fagan, Anne M.; Molinuevo, José Luis; Jansen, Willemijn J.; Winblad, Bengt; Shaw, Leslie M.; Andreasson, Ulf; Otto, Markus; Mollenhauer, Brit; Wiltfang, Jens; Turner, Martin R.; Zerr, Inga; Handels, Ron; Thompson, Alexander G.; Johansson, Gunilla; Ermann, Natalia; Trojanowski, John Q.; Karaca, Ilker; Wagner, Holger; Oeckl, Patrick; van Waalwijk van Doorn, Linda; Bjerke, Maria; Kapogiannis, Dimitrios; Kuiperij, H. Bea; Farotti, Lucia; Li, Yi; Gordon, Brian A.; Epelbaum, Stéphane; Vos, Stephanie J.B.; Klijn, Catharina J.M.; Van Nostrand, William E.; Minguillon, Carolina; Schmitz, Matthias; Gallo, Carla; Lopez Mato, Andrea; Thibaut, Florence; Lista, Simone; Alcolea, Daniel; Zetterberg, Henrik; Blennow, Kaj; Kornhuber, JohannesIn the 12 years since the publication of the first Consensus Paper of the WFSBP on biomarkers of neurodegenerative dementias, enormous advancement has taken place in the field, and the Task Force takes now the opportunity to extend and update the original paper. New concepts of Alzheimer's disease (AD) and the conceptual interactions between AD and dementia due to AD were developed, resulting in two sets for diagnostic/research criteria. Procedures for pre-analytical sample handling, biobanking, analyses and post-analytical interpretation of the results were intensively studied and optimised. A global quality control project was introduced to evaluate and monitor the inter-centre variability in measurements with the goal of harmonisation of results. Contexts of use and how to approach candidate biomarkers in biological specimens other than cerebrospinal fluid (CSF), e.g. blood, were precisely defined. Important development was achieved in neuroimaging techniques, including studies comparing amyloid-β positron emission tomography results to fluid-based modalities. Similarly, development in research laboratory technologies, such as ultra-sensitive methods, raises our hopes to further improve analytical and diagnostic accuracy of classic and novel candidate biomarkers. Synergistically, advancement in clinical trials of anti-dementia therapies energises and motivates the efforts to find and optimise the most reliable early diagnostic modalities. Finally, the first studies were published addressing the potential of cost-effectiveness of the biomarkers-based diagnosis of neurodegenerative disorders.Item Current state of Alzheimer's fluid biomarkers(Springer, 2018-11-28) Molinuevo, José Luis; Ayton, Scott; Batrla, Richard; Bednar, Martin M.; Bittner, Tobias; Cummings, Jeffrey; Fagan, Anne M.; Hampel, Harald; Mielke, Michelle M.; Mikulskis, Alvydas; O'Bryant, Sid E.; Scheltens, Philip; Sevigny, Jeffrey; Shaw, Leslie M.; Soares, Holly D.; Tong, Gary; Trojanowski, John Q.; Zetterberg, Henrik; Blennow, KajAlzheimer's disease (AD) is a progressive neurodegenerative disease with a complex and heterogeneous pathophysiology. The number of people living with AD is predicted to increase; however, there are no disease-modifying therapies currently available and none have been successful in late-stage clinical trials. Fluid biomarkers measured in cerebrospinal fluid (CSF) or blood hold promise for enabling more effective drug development and establishing a more personalized medicine approach for AD diagnosis and treatment. Biomarkers used in drug development programmes should be qualified for a specific context of use (COU). These COUs include, but are not limited to, subject/patient selection, assessment of disease state and/or prognosis, assessment of mechanism of action, dose optimization, drug response monitoring, efficacy maximization, and toxicity/adverse reactions identification and minimization. The core AD CSF biomarkers Aβ42, t-tau, and p-tau are recognized by research guidelines for their diagnostic utility and are being considered for qualification for subject selection in clinical trials. However, there is a need to better understand their potential for other COUs, as well as identify additional fluid biomarkers reflecting other aspects of AD pathophysiology. Several novel fluid biomarkers have been proposed, but their role in AD pathology and their use as AD biomarkers have yet to be validated. In this review, we summarize some of the pathological mechanisms implicated in the sporadic AD and highlight the data for several established and novel fluid biomarkers (including BACE1, TREM2, YKL-40, IP-10, neurogranin, SNAP-25, synaptotagmin, ɑ-synuclein, TDP-43, ferritin, VILIP-1, and NF-L) associated with each mechanism. We discuss the potential COUs for each biomarker.Item Diversified use of Non-invasive Biomarkers in Study Protocol and Screen failure in Non-Alcoholic Steatohepatitis (NASH)(2023-05) Masaye, Nikita P.; Gregory, PaulaThis study examines how non-invasive biomarkers of NASH are introduced into the study protocol and whether this has an impact on screen failure. The study will investigate the use of non-invasive biomarkers in the design of study protocols for NASH drug trials and will also examine if screening approaches established using non-invasive biomarkers can reduce screen failure.Item Identifying Potential Biomarkers and Clinical Trial Outcomes for Future Clinical Trials for SLC13A5 Deficiency(2022-12) Cooper, Sydney; Simecka, Jerry W.; Cihlar, Jennifer C.Item Liver Biomarkers and Lipid Profiles in Mexican and Mexican-American 10- to 14-Year-Old Adolescents at Risk for Type 2 Diabetes(Hindawi, 2017-07-26) Fernández-Gaxiola, Ana Cecilia; Valdés-Ramos, Roxana; Fulda, Kimberly G.; López, Ana Laura Guadarrama; Martínez-Carrillo, Beatriz E.; Franks, Susan F.; Fernando, Shane I.Liver enzymes alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) are markers for type 2 diabetes mellitus (T2DM); alkaline phosphatase is a marker of liver disease. Mexican-American adolescents are disproportionately affected by T2DM, while in Mexico its prevalence is emerging. We assessed liver biomarkers and lipid profiles among Mexican and Mexican-American adolescents 10-14 years old with high/low risk of T2DM through a cross-sectional, descriptive study (Texas n = 144; Mexico n = 149). We included family medical histories, anthropometry, and blood pressure. Obesity was present in one-third of subjects in both sites. ALT (UL) was higher (p < 0.001) in high-risk adolescents (23.5 ± 19.5 versus 17.2 ± 13.4 for males, 19.7 ± 11.6 versus 15.1 ± 5.5 for females), in Toluca and in Texas (26.0 ± 14.7 versus 20.0 ± 13.2 for males, 18.2 ± 13.4 versus 14.6 ± 10.1 for females), as well as GGT (UL) (p < 0.001) (18.7 ± 11.1 versus 12.4 ± 2.3 for males, 13.6 ± 5.8 versus 11.5 ± 3.9 for Mexican females; 21.0 ± 6.8 versus 15.4 ± 5.5 for males, 14.3 ± 5.0 versus 13.8 ± 5.3 for females in Texas). We found no differences by sex or BMI. Total cholesterol and HDL were higher among Mexican-Americans (p < 0.001). In conclusion, multiple risk factors were present in the sample. We found differences by gender and between high and low risk for T2DM adolescents in all liver enzymes in both sites.Item Neurodegeneration from the AT(N) framework is different among Mexican Americans compared to non-Hispanic Whites: A Health & Aging Brain among Latino Elders (HABLE) Study(Wiley Periodicals, LLC, 2022-02-09) O'Bryant, Sid E.; Zhang, Fan; Petersen, Melissa E.; Hall, James R.; Johnson, Leigh A.; Yaffe, Kristine; Braskie, Meredith N.; Rissman, Robert A.; Vig, Rocky; Toga, Arthur W.Introduction: We sought to examine a magnetic resonance imaging (MRI)-based marker of neurodegeneration from the AT(N) (amyloid/tau/neurodegeneration) framework among a multi-ethnic, community-dwelling cohort. Methods: Community-dwelling Mexican Americans and non-Hispanic White adults and elders were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing and 3T MRI of the brain. A neurodegeneration MRI meta-region of interest (ROI) biomarker for the AT(N) framework was calculated. Results: Data were examined from n = 1305 participants. Mexican Americans experienced N at significantly younger ages. The N biomarker was significantly associated with cognitive outcomes. N was significantly impacted by cardiovascular factors (e.g., total cholesterol, low-density lipoprotein) among non-Hispanic Whites whereas diabetes (glucose, HbA1c, duration of diabetes) and sociocultural (household income, acculturation) factors were strongly associated with N among Mexican Americans. Discussion: The prevalence, progression, timing, and sequence of the AT(N) biomarkers must be examined across diverse populations.Item Protein Biomakers of Estrogenic Impact on Mouse and Rat Uterus(2021-05) Thai, Stephen Duy-An; Prokai, Laszlo; Prokai-Tatrai, Katalin; Lacko, Andras G.Understanding the structural and morphological impact that occur in the uterus upon exposure to estrogens can reveal how these hormones elicit changes in the organ. This study seeks to revalidate the data obtained in studies of ovariectomized mice and rats treated with 17β-estradiol, followed by comparative analysis of the protein expression between the two animal models (the mice model studied by Prokai et al. [1] and the rat model presented in a dissertation by Rahlouni [2]). During these studies, female Swiss-Webster mice and Sprague-Dawley rats were ovariectomized (OVX) and divided respectively into two groups: 1) The control was treated with a corn oil vehicle while 2) The treatment group received 17β-estradiol injection for 5 days. Raw data gathered from the earlier proteomics studies were reanalyzed using Maxquant version 1.6.17, which utilized extracted ion chromatography technique (XIC). LFQ analyst and Ingenuity Pathway Analysis (IPA) version 5.0 were used to identify proteins that were differentially regulated by 17β-estradiol and perform comparative analyses of the protein expression between OVX mice and rats. Reanalysis of OVX mice identified 59 proteins of interest at 95% confidence with 29 upregulated and 30 downregulated significantly. Reanalysis of the OVX rats identified 126 differentially expressed proteins at 95% confidence with 98 upregulated and 27 downregulated significantly. Comparative analysis using IPA® found 27 proteins unique to mice and 85 proteins unique to rats. Conversely, the OVX mice and rats shared 19 proteins regulated by 17β-estradiol in the uterus. Ingenuity Pathway Analysis® also created networks in OVX mouse and rat models showing a relationship with estrogen receptors in the nucleus, which can bind 17β-estradiol and then initiate gene transcription. Although there is overlap between OVX mice and rat protein expression, the proteins that were found to be unique to each animal demonstrate that a complementary model using both animals provides a much broader view of uterine protein expression in OVX animals treated with 17?-estradiol. Additionally, this study illustrates the merit of reanalyzing older data with improved computational and bioinformatic tools to pinpoint proteins of interest for future analysis as potential markers of estrogenic effects in the uterus.Item Proteomic profiles of prevalent mild cognitive impairment and Alzheimer's disease among adults with Down syndrome(Wiley Periodicals, Inc., 2020-04-17) Petersen, Melissa E.; Zhang, Fan; Krinsky-McHale, Sharon J.; Silverman, Wayne; Lee, Joseph H.; Pang, Deborah; Hall, James R.; Schupf, Nicole; O'Bryant, Sid E.Introduction: We sought to determine if a proteomic profile approach developed to detect Alzheimer's disease (AD) in the general population would apply to adults with Down syndrome (DS). Methods: Plasma samples were obtained from 398 members of a community-based cohort of adults with DS. A total of n = 186 participants were determined to be non-demented and without mild cognitive impairment (MCI) at baseline and throughout follow-up; n = 50 had prevalent MCI; n = 42 had prevalent AD. Results: The proteomic profile yielded an area under the curve (AUC) of 0.92, sensitivity (SN) = 0.80, and specificity (SP) = 0.98 detecting prevalent MCI. For detecting prevalent AD, the proteomic profile yielded an AUC of 0.89, SN = 0.81, and SP = 0.97. The overall profile closely resembled our previously published profile of AD in the general population. Discussion: These data provide evidence of the applicability of our blood-based algorithm for detecting MCI/AD among adults with DS.Item The Health & Aging Brain among Latino Elders (HABLE) study methods and participant characteristics(Wiley Periodicals, LLC, 2021-06-21) O'Bryant, Sid E.; Johnson, Leigh A.; Barber, Robert C.; Braskie, Meredith N.; Christian, Bradley; Hall, James R.; Hazra, Nalini; King, Kevin; Kothapalli, Deydeep; Large, Stephanie; Mason, David; Matsiyevskiy, Elizabeth; McColl, Roderick; Nandy, Rajesh; Palmer, Raymond; Petersen, Melissa E.; Philips, Nicole; Rissman, Robert A.; Shi, Yonggang; Toga, Arthur W.; Vintimilla, Raul; Vig, Rocky; Zhang, Fan; Yaffe, KristineIntroduction: Mexican Americans remain severely underrepresented in Alzheimer's disease (AD) research. The Health & Aging Brain among Latino Elders (HABLE) study was created to fill important gaps in the existing literature. Methods: Community-dwelling Mexican Americans and non-Hispanic White adults and elders (age 50 and above) were recruited. All participants underwent comprehensive assessments including an interview, functional exam, clinical labs, informant interview, neuropsychological testing, and 3T magnetic resonance imaging (MRI) of the brain. Amyloid and tau positron emission tomography (PET) scans were added at visit 2. Blood samples were stored in the Biorepository. Results: Data was examined from n = 1705 participants. Significant group differences were found in medical, demographic, and sociocultural factors. Cerebral amyloid and neurodegeneration imaging markers were significantly different between Mexican Americans and non-Hispanic Whites. Discussion: The current data provide strong support for continued investigations that examine the risk factors for and biomarkers of AD among diverse populations.Item The Role of Estriol and Estrone in Keratoconic Stromal Sex Hormone Receptors(MDPI, 2022-01-14) Escandon, Paulina; Nicholas, Sarah E.; Cunningham, Rebecca L.; Murphy, David A.; Riaz, Kamran M.; Karamichos, DimitriosKeratoconus (KC) is a progressive corneal thinning disease that manifests in puberty and worsens during pregnancy. KC onset and progression are attributed to diverse factors that include: environmental, genetics, and hormonal imbalances; however, the pathobiology remains elusive. This study aims to determine the role of corneal stroma sex hormone receptors in KC and their interplay with estrone (E1) and estriol (E3) using our established 3D in vitro model. Healthy cornea stromal cells (HCFs) and KC cornea stromal cells (HKCs), both male and female, were stimulated with various concentrations of E1 and E3. Significant changes were observed between cell types, as well as between males and females in the sex hormone receptors tested; androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERalpha), and estrogen receptor beta (ERbeta) using Western blot analysis. E1 and E3 stimulations in HCF females showed AR, PR, and ERbeta were significantly upregulated compared to HCF males. In contrast, ERalpha and ERbeta had significantly higher expression in HKC's females than HKC's males. Our data suggest that the human cornea is a sex-dependent, hormone-responsive tissue that is significantly influenced by E1 and E3. Therefore, it is plausible that E1, E3, and sex hormone receptors are involved in the KC pathobiology, warranting further investigation.