Comparison of Serum Triiodothyronine with Biomarkers for Alzheimer’s Disease Continuum in Euthyroid Subjects

2021 ◽  
pp. 1-10
Author(s):  
Feifei Ge ◽  
Lin Dong ◽  
Donglin Zhu ◽  
Xingjian Lin ◽  
Jingping Shi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Characteristic Curve ◽  
Amyloid Β ◽  
Diagnostic Value ◽  
Thyroid Stimulating Hormone ◽  
Csf Biomarkers ◽  
Free Triiodothyronine ◽  
Diagnostic Significance ◽  
Cross Sectional

Background: Accumulating studies have implicated thyroid dysfunction in the pathogenesis of Alzheimer’s disease (AD). Objective: This study aimed to explore the association between thyroid hormone (TH) levels and cerebrospinal fluid (CSF) biomarkers for AD continuum among euthyroid subjects. Methods: In all, 93 clinically euthyroid subjects with a cognitive decline were included in this prospective cross-sectional study and were divided into groups with abnormal AD biomarkers (belonging to the “Alzheimer’s continuum”; A+ patients) and those with “normal AD biomarkers” or “non-AD pathological changes” (A–patients), according to the ATN research framework classification for AD. A partial correlation analysis of serum thyroid-stimulating hormone (TSH) or TH levels with CSF biomarkers was conducted. The predictor for A+ patients was analyzed via binary logistic regressions. Finally, the diagnostic significance of individual biochemical predictors for A+ patients was estimated via receiver operating characteristic curve analysis. Results: Serum total triiodothyronine (TT3) and free triiodothyronine (FT3) levels were found to affect the levels of CSF amyloid-β (Aβ)42 and the ratios of Aβ 42/40. Further, FT3 was found to be a significant predictor for A+ via binary logistic regression modeling. Moreover, FT3 showed a high diagnostic value for A+ in euthyroid subjects. Conclusion: Even in a clinical euthyroid state, low serum FT3 and TT3 levels appear to be differentially associated with AD-specific CSF changes. These data indicate that serum FT3 is a strong candidate for differential diagnosis between AD continuum and non-AD dementia, which benefits the early diagnosis and effective management of preclinical and clinical AD patients.

scholarly journals Plasma neurofilament light is associated with white matter damage in Alzheimer's disease

2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Balabandian ◽  
Mohammad Reza Rostami ◽  
Samuel Berchi Kankam ◽  
Fetemeh Ranjbaran ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Diffusion Tensor ◽  
Amyloid Β ◽  
Brain Regions ◽  
Csf Biomarkers ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Microstructural Changes

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration, and synaptic damage in AD. However, few investigations have been carried out on the association between plasma NFL and white matter microstructure integrity. We have investigated the cross-sectional associations of plasma NFL, CSF total tau, phosphorylated tau, and Amyloid β with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, separately using a partial correlation model controlled for the effect of age, sex, and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL negatively correlates with FA and the positive correlation with RD, DA, and MD values in different regions. Our findings showed that plasma NFL is associated with white matter changes and AD-related features, including atrophy and hypometabolism. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and MCI progression to AD.

scholarly journals Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Jonathan D. Drake ◽  
Alison B. Chambers ◽  
Brian R. Ott ◽  
Lori A. Daiello ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Intercellular Adhesion Molecule ◽  
Csf Biomarkers ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: Cerebrovascular dysfunction confers risk for functional decline in Alzheimer’s disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood. Objective: We utilized Alzheimer’s Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD. Methods: Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal). We further analyzed associations of these biomarkers with brain-based AD biomarkers in a subset with available cerebrospinal fluid (CSF) data (n = 351). p-values derived from main effects and interaction terms from the linear regressions were used to assess the relationship between independent and dependent variables for significance (significance level was set at 0.05 a priori for all analysis). Results: Higher mean VCAM-1 (p = 0.0026) and ICAM-1 (p = 0.0189) levels were found in AD versus MCI groups; however, not in MCI versus cognitively normal groups. Only VCAM-1 was linked with CDR-SB scores (p = 0.0157), and APOE ɛ4 genotype modified this effect. We observed independent, additive associations when VCAM-1 and CSF amyloid-β (Aβ 42), total tau, phosphorylated tau (P-tau), or P-tau/Aβ 42 (all <  p = 0.01) were combined in a CDR-SB model; ICAM-1 showed a similar pattern, but to a lesser extent. Conclusion: Our findings indicate independent associations of plasma-based vascular biomarkers and CSF biomarkers with AD-related clinical impairment.

scholarly journals Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Current Evidence and Future Perspectives

2021 ◽  
Vol 11 (2) ◽  
pp. 215
Author(s):  
Donovan A. McGrowder ◽  
Fabian Miller ◽  
Kurt Vaz ◽  
Chukwuemeka Nwokocha ◽  
Cameil Wilson-Clarke ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Late Onset ◽  
Amyloid Β ◽  
Current Evidence ◽  
Csf Biomarkers ◽  
Diagnostic Efficacy ◽  
Neurofilament Light ◽  
New Biomarkers

Alzheimer’s disease is a progressive, clinically heterogeneous, and particularly complex neurodegenerative disease characterized by a decline in cognition. Over the last two decades, there has been significant growth in the investigation of cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease. This review presents current evidence from many clinical neurochemical studies, with findings that attest to the efficacy of existing core CSF biomarkers such as total tau, phosphorylated tau, and amyloid-β (Aβ42), which diagnose Alzheimer’s disease in the early and dementia stages of the disorder. The heterogeneity of the pathophysiology of the late-onset disease warrants the growth of the Alzheimer’s disease CSF biomarker toolbox; more biomarkers showing other aspects of the disease mechanism are needed. This review focuses on new biomarkers that track Alzheimer’s disease pathology, such as those that assess neuronal injury (VILIP-1 and neurofilament light), neuroinflammation (sTREM2, YKL-40, osteopontin, GFAP, progranulin, and MCP-1), synaptic dysfunction (SNAP-25 and GAP-43), vascular dysregulation (hFABP), as well as CSF α-synuclein levels and TDP-43 pathology. Some of these biomarkers are promising candidates as they are specific and predict future rates of cognitive decline. Findings from the combinations of subclasses of new Alzheimer’s disease biomarkers that improve their diagnostic efficacy in detecting associated pathological changes are also presented.

scholarly journals Diagnosing Alzheimer’s Disease from Circulating Blood Leukocytes Using a Fluorescent Amyloid Probe

2021 ◽  
pp. 1-14
Author(s):  
Stefanie A.G. Black ◽  
Anastasiia A. Stepanchuk ◽  
George W. Templeton ◽  
Yda Hernandez ◽  
Tomoko Ota ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Misfolding ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Blood Leukocytes ◽  
Peripheral Blood Mononuclear ◽  
The Brain

Background: Toxic amyloid-β (Aβ) peptides aggregate into higher molecular weight assemblies and accumulate not only in the extracellular space, but also in the walls of blood vessels in the brain, increasing their permeability, and promoting immune cell migration and activation. Given the prominent role of the immune system, phagocytic blood cells may contact pathological brain materials. Objective: To develop a novel method for early Alzheimer’s disease (AD) detection, we used blood leukocytes, that could act as “sentinels” after trafficking through the brain microvasculature, to detect pathological amyloid by labelling with a conformationally-sensitive fluorescent amyloid probe and imaging with confocal spectral microscopy. Methods: Formalin-fixed peripheral blood mononuclear cells (PBMCs) from cognitively healthy control (HC) subjects, mild cognitive impairment (MCI) and AD patients were stained with the fluorescent amyloid probe K114, and imaged. Results were validated against cerebrospinal fluid (CSF) biomarkers and clinical diagnosis. Results: K114-labeled leukocytes exhibited distinctive fluorescent spectral signatures in MCI/AD subjects. Comparing subjects with single CSF biomarker-positive AD/MCI to negative controls, our technique yielded modest AUCs, which improved to the 0.90 range when only MCI subjects were included in order to measure performance in an early disease state. Combining CSF Aβ 42 and t-Tau metrics further improved the AUC to 0.93. Conclusion: Our method holds promise for sensitive detection of AD-related protein misfolding in circulating leukocytes, particularly in the early stages of disease.

scholarly journals New fluid biomarkers tracking non-amyloid-β and non-tau pathology in Alzheimer’s disease

2020 ◽  
Vol 52 (4) ◽  
pp. 556-568 ◽  
Author(s):  
Sun Ah Park ◽  
Song Mi Han ◽  
Chae Eun Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Response ◽  
Amyloid Β ◽  
Clinical Severity ◽  
Intercellular Adhesion Molecule ◽  
Csf Biomarkers ◽  
Tau Pathology ◽  
Protein Clearance ◽  
New Biomarkers

Abstract Cerebrospinal fluid (CSF) biomarkers based on the core pathological proteins associated with Alzheimer’s disease (AD), i.e., amyloid-β (Aβ) and tau protein, are widely regarded as useful diagnostic biomarkers. However, a lack of biomarkers for monitoring the treatment response and indexing clinical severity has proven to be problematic in drug trials targeting Aβ. Therefore, new biomarkers are needed to track non-Aβ and non-tau pathology. Many proteins involved in the pathophysiological progression of AD have shown promise as new biomarkers. Neurodegeneration- and synapse-related biomarkers in CSF (e.g., neurofilament light polypeptide [NFL], neurogranin, and visinin-like protein 1) and blood (e.g., NFL) aid prediction of AD progress, as well as early diagnosis. Neuroinflammation, lipid dysmetabolism, and impaired protein clearance are considered important components of AD pathophysiology. Inflammation-related proteins in the CSF, such as progranulin, intercellular adhesion molecule 1, and chitinase-3-like protein 1 (YKL-40), are useful for the early detection of AD and can represent clinical severity. Several lipid metabolism-associated biomarkers and protein clearance-linked markers have also been suggested as candidate AD biomarkers. Combinations of subsets of new biomarkers enhance their utility in terms of broadly characterizing AD-associated pathological changes, thereby facilitating precise selection of susceptible patients and comprehensive monitoring of the treatment response. This approach could facilitate the development of effective treatments for AD.

scholarly journals CSF biomarkers of Alzheimer's disease concord with amyloid-β PET and predict clinical progression: A study of fully automated immunoassays in BioFINDER and ADNI cohorts

2018 ◽  
Vol 14 (11) ◽  
pp. 1470-1481 ◽  
Author(s):  
Oskar Hansson ◽  
John Seibyl ◽  
Erik Stomrud ◽  
Henrik Zetterberg ◽  
John Q. Trojanowski ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Clinical Progression

scholarly journals Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment

2015 ◽  
Vol 36 (3) ◽  
pp. 621-628 ◽  
Author(s):  
Sara Shams ◽  
Tobias Granberg ◽  
Juha Martola ◽  
Xiaozhen Li ◽  
Mana Shams ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Serum Albumin ◽  
Amyloid Β ◽  
Cerebral Microbleeds ◽  
Csf Biomarkers ◽  
Barrier Dysfunction ◽  
T Tau

Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer’s disease and mild cognitive impairment ( p < 0.05). CSF/serum albumin ratios were high with multiple CMBs ( p < 0.001), reflecting accompanying blood–brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer’s patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer’s disease ( p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.

scholarly journals Plasma neurofilament light and cerebrospinal fluid biomarkers are associated with white matter damage in Alzheimer's disease

2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Balabandian ◽  
Mohammad Reza Rostami ◽  
Samuel Berchi Kankam
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
White Matter ◽  
Diffusion Tensor ◽  
Brain Regions ◽  
Csf Biomarkers ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Microstructural Changes ◽  
Cerebrospinal Fluid Biomarkers

Abstract The most replicated blood biomarker for monitoring Alzheimer’s disease is neurofilament light (NFL). Recent evidence revealed that the plasma level of the NFL has a strong predictive value in cognitive decline and is elevated in AD patients. The Diffusion Tensor Imaging (DTI) is understood to reflect white matter disruption, neurodegeneration largely, and synaptic damage in AD. However, there is no investigation of the association between plasma NFL and white matter microstructure integrity. we have investigated the cross-sectional associations of plasma NFL, CSF tau, p tau, and Aβ with white matter microstructural changes as measured by DTI in 92 mild cognitive impairment (MCI) participants. We investigated potential correlations of the DTI values of each region of the MNI atlas, with plasma NFL, CSF total tau, CSF p tau, and as well as CSF Aβ, separately using a partial correlation model controlled for the effect of age, sex and APOE ε4 genotype. Our findings revealed a significant correlation between plasma and CSF biomarkers with altered white matter microstructural changes in widespread brain regions. Plasma NFL has a negative correlation with FA and positive correlation with RD, AD, and MD values in different regions. Plasma NFL promises to be an early biomarker of microstructural changes in MCI and for MCI progression to AD.

scholarly journals Longitudinal Observation of Early-Onset Alzheimer’s Disease Dementia with Positive CSF Biomarkers/Negative Amyloid-β Positron-Emission Tomography

2021 ◽  
Vol 39 (3) ◽  
pp. 214-218
Author(s):  
Min Hye Kim ◽  
Joonho Lee ◽  
Hong Nam Kim ◽  
In Ja Shin ◽  
Keun Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Early Onset ◽  
Brain Magnetic Resonance Imaging ◽  
Amyloid Β ◽  
Emission Tomography ◽  
Csf Biomarkers ◽  
Amyloid Pet ◽  
Positron Emission

We report a 61-year-old woman with clinical course for Alzheimer’s disease (AD) dementia and discordant amyloid-β positron-emission tomography (PET) and cerebrospinal fluid biomarkers. Brain magnetic resonance imaging revealed remarkable atrophy in the hippocampus. However, repeated delayed <sup>18</sup>F-flutemetamol brain amyloid PET images with 1 year-interval revealed no amyloid deposition, whereas her CSF revealed low Aβ42, high total tau and p-tau181. This discordant amyloid-β PET and CSF biomarkers in this early-onset AD dementia might be associated with her low resilience or mixed pathology.

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