7 research outputs found
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The Alzheimer's Biomarker Consortium-Down Syndrome: Rationale and methodology.
INTRODUCTION: Adults with Down syndrome (DS) are at exceptionally high risk for Alzheimer's disease (AD), with virtually all individuals developing key neuropathological features by age 40. Identifying biomarkers of AD progression in DS can provide valuable insights into pathogenesis and suggest targets for disease modifying treatments. METHODS: We describe the development of a multi-center, longitudinal study of biomarkers of AD in DS. The protocol includes longitudinal examination of clinical, cognitive, blood and cerebrospinal fluid-based biomarkers, magnetic resonance imaging and positron emission tomography measures (at 16-month intervals), as well as genetic modifiers of AD risk and progression. RESULTS: Approximately 400 individuals will be enrolled in the study (more than 370 to date). The methodological approach from the administrative, clinical, neuroimaging, omics, neuropathology, and statistical cores is provided. DISCUSSION: This represents the largest U.S.-based, multi-site, biomarker initiative of AD in DS. Findings can inform other multidisciplinary networks studying AD in the general population
Plasma Biomarkers of Alzheimers Disease Are Associated with Physical Functioning Outcomes Among Cognitively Normal Adults in the Multiethnic HABS-HD Cohort.
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Plasma Biomarkers of Alzheimers Disease Are Associated with Physical Functioning Outcomes Among Cognitively Normal Adults in the Multiethnic HABS-HD Cohort.
In this study, we examined the link between plasma Alzheimers disease (AD) biomarkers and physical functioning outcomes within a community-dwelling, multiethnic cohort. Data from 1 328 cognitively unimpaired participants (n = 659 Mexican American and n = 669 non-Hispanic White) from the ongoing Health & Aging Brain Study-Health Disparities (HABS-HD) cohort were examined. Plasma AD biomarkers (amyloid beta [Aβ]40, Aβ42, total tau [t-tau], and neurofilament light chain [NfL]) were assayed using the ultra-sensitive Simoa platform. Physical functioning measures were the Timed Up and Go (TUG) and the Short Physical Performance Battery (SPPB). Cross-sectional linear regression analyses revealed that plasma Aβ 40 (p < .001), Aβ 42 (p = .003), and NfL (p < .001) were each significantly associated with TUG time in seconds. Plasma Aβ 40 (p < .001), Aβ 42 (p < .001), t-tau (p = .002), and NfL (p < .001) were each significantly associated with SPPB Total Score. Additional analyses demonstrate that the link between plasma AD biomarkers and physical functioning outcomes were strongest among Mexican Americans. Plasma AD biomarkers are receiving a great deal of attention in the literature and are now available clinically including use in clinical trials. The examination of AD biomarkers and physical functioning may allow for the development of risk profiles, which could stratify a persons risk for neurodegenerative diseases, such as AD, based on plasma AD biomarkers, physical functioning, ethnicity, or a combination of these measures prior to the onset of cognitive impairment
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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.
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
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Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome.
INTRODUCTION: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimers disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS. METHODS: T1-weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory. RESULTS: Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory. DISCUSSION: The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS
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Probing the proteome to explore potential correlates of increased Alzheimers-related cerebrovascular disease in adults with Down syndrome.
Cerebrovascular disease is associated with symptoms and pathogenesis of Alzheimers disease (AD) among adults with Down syndrome (DS). The cause of increased dementia-related cerebrovascular disease in DS is unknown. We explored whether protein markers of neuroinflammation are associated with markers of cerebrovascular disease among adults with DS. Participants from the Alzheimers disease in Down syndrome (ADDS) study with magnetic resonance imaging (MRI) scans and blood biomarker data were included. Support vector machine (SVM) analyses examined the relationship of blood-based proteomic biomarkers with MRI-defined cerebrovascular disease among participants characterized as having cognitive decline (n = 36, mean age ± SD = 53 ± 6.2) and as being cognitively stable (n = 78, mean age = 49 ± 6.4). Inflammatory and AD markers were associated with cerebrovascular disease, particularly among symptomatic individuals. The pattern suggested relatively greater inflammatory involvement among cognitively stable individuals and greater AD involvement among those with cognitively decline. The findings help to generate hypotheses that both inflammatory and AD markers are implicated in cerebrovascular disease among those with DS and point to potential mechanistic pathways for further examination