scholarly journals Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer’s disease in adults with Down syndrome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alberto Lleó ◽  
Henrik Zetterberg ◽  
Jordi Pegueroles ◽  
Thomas K. Karikari ◽  
María Carmona-Iragui ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Single Molecule ◽  
Area Under The Curve ◽  
Imaging Biomarkers ◽  
Potential Biomarker ◽  
Prodromal Ad ◽  
Asymptomatic Individuals ◽  
The Relationship

AbstractPlasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer’s disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73–0.87] and 0.92 [95% CI 0.89–0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS.

scholarly journals Plasma contact factors as novel biomarkers for diagnosing Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jung Eun Park ◽  
Do Sung Lim ◽  
Yeong Hee Cho ◽  
Kyu Yeong Choi ◽  
Jang Jae Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Stage ◽  
Area Under The Curve ◽  
Contact System ◽  
Plasma Diagnostic ◽  
Vascular Abnormalities ◽  
Prodromal Ad ◽  
Novel Biomarkers

Abstract Background Alzheimer’s disease (AD) is the most common cause of dementia and most of AD patients suffer from vascular abnormalities and neuroinflammation. There is an urgent need to develop novel blood biomarkers capable of diagnosing Alzheimer’s disease (AD) at very early stage. This study was performed to find out new accurate plasma diagnostic biomarkers for AD by investigating a direct relationship between plasma contact system and AD. Methods A total 101 of human CSF and plasma samples from normal and AD patients were analyzed. The contact factor activities in plasma were measured with the corresponding specific peptide substrates. Results The activities of contact factors (FXIIa, FXIa, plasma kallikrein) and FXa clearly increased and statistically correlated as AD progresses. We present here, for the first time, the FXIIa cut-off scores to as: > 26.3 U/ml for prodromal AD [area under the curve (AUC) = 0.783, p < 0.001] and > 27.2 U/ml for AD dementia (AUC = 0.906, p < 0.001). We also describe the cut-off scores from the ratios of CSF Aβ1–42 versus the contact factors. Of these, the representative ratio cut-off scores of Aβ1–42/FXIIa were to be: < 33.8 for prodromal AD (AUC = 0.965, p < 0.001) and < 27.44 for AD dementia (AUC = 1.0, p < 0.001). Conclusion The activation of plasma contact system is closely associated with clinical stage of AD, and FXIIa activity as well as the cut-off scores of CSF Aβ1–42/FXIIa can be used as novel accurate diagnostic AD biomarkers.

scholarly journals To Explore the Predictive Power of Visuomotor Network Dysfunctions in Mild Cognitive Impairment and Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Justine Staal ◽  
Francesco Mattace-Raso ◽  
Hennie A. M. Daniels ◽  
Johannes van der Steen ◽  
Johan J. M. Pel
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Support Vector Machine ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Predictive Power ◽  
Area Under The Curve ◽  
Classification Performance ◽  
Support Vector ◽  
Potential Biomarker

BackgroundResearch into Alzheimer’s disease has shifted toward the identification of minimally invasive and less time-consuming modalities to define preclinical stages of Alzheimer’s disease.MethodHere, we propose visuomotor network dysfunctions as a potential biomarker in AD and its prodromal stage, mild cognitive impairment with underlying the Alzheimer’s disease pathology. The functionality of this network was tested in terms of timing, accuracy, and speed with goal-directed eye-hand tasks. The predictive power was determined by comparing the classification performance of a zero-rule algorithm (baseline), a decision tree, a support vector machine, and a neural network using functional parameters to classify controls without cognitive disorders, mild cognitive impaired patients, and Alzheimer’s disease patients.ResultsFair to good classification was achieved between controls and patients, controls and mild cognitive impaired patients, and between controls and Alzheimer’s disease patients with the support vector machine (77–82% accuracy, 57–93% sensitivity, 63–90% specificity, 0.74–0.78 area under the curve). Classification between mild cognitive impaired patients and Alzheimer’s disease patients was poor, as no algorithm outperformed the baseline (63% accuracy, 0% sensitivity, 100% specificity, 0.50 area under the curve).Comparison with Existing Method(s)The classification performance found in the present study is comparable to that of the existing CSF and MRI biomarkers.ConclusionThe data suggest that visuomotor network dysfunctions have potential in biomarker research and the proposed eye-hand tasks could add to existing tests to form a clear definition of the preclinical phenotype of AD.

scholarly journals Circuitry and Synaptic Dysfunction in Alzheimer’s Disease: A New Tau Hypothesis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Siddhartha Mondragón-Rodríguez ◽  
Humberto Salgado-Burgos ◽  
Fernando Peña-Ortega
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Connectivity ◽  
Aspartate Receptor ◽  
Potential Biomarker ◽  
Prodromal Ad ◽  
Brain Circuit ◽  
New Evidence ◽  
Ad Mouse Model

For more than five decades, the field of Alzheimer’s disease (AD) has focused on two main hypotheses positing amyloid-beta (Aβ) and Tau phosphorylation (pTau) as key pathogenic mediators. In line with these canonical hypotheses, several groups around the world have shown that the synaptotoxicity in AD depends mainly on the increase in pTau levels. Confronting this leading hypothesis, a few years ago, we reported that the increase in phosphorylation levels of dendritic Tau, at its microtubule domain (MD), acts as a neuroprotective mechanism that prevents N-methyl-D-aspartate receptor (NMDAr) overexcitation, which allowed us to propose that Tau protein phosphorylated near MD sites is involved in neuroprotection, rather than in neurodegeneration. Further supporting this alternative role of pTau, we have recently shown that early increases in pTau close to MD sites prevent hippocampal circuit overexcitation in a transgenic AD mouse model. Here, we will synthesize this new evidence that confronts the leading Tau-based AD hypothesis and discuss the role of pTau modulating neural circuits and network connectivity. Additionally, we will briefly address the role of brain circuit alterations as a potential biomarker for detecting the prodromal AD stage.

Physical Activity and Cognitive and Imaging Biomarkers of Alzheimer's Disease in Down Syndrome

2021 ◽  
Author(s):  
Victoria Fleming ◽  
Brianna Piro-Gambetti ◽  
Austin Patrick ◽  
Matthew Zammit ◽  
Andrew Alexander ◽  
...  
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Imaging Biomarkers

scholarly journals Cerebrospinal Fluid α-Synuclein Predicts Neurodegeneration and Clinical Progression in Prodromal Alzheimer's Disease

2020 ◽  
Author(s):  
Jie-Qiong Li ◽  
Yan-Lin Bi ◽  
Xue-Ning Shen ◽  
Hui-Fu Wang ◽  
Wei Xu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Characteristic Curve ◽  
Longitudinal Change ◽  
Clinical Progression ◽  
Chinese Han ◽  
Predictive Values ◽  
Potential Biomarker ◽  
Prodromal Ad

Abstract BackgroundAccumulating reports suggest that α-synuclein is involved in Alzheimer disease (AD) pathogenesis. Cerebrospinal fluid (CSF) α-synuclein could be a potential biomarker of AD. We sought to test whether CSF α-synuclein is associated with other AD biomarkers and could predict neurodegeneration and clinical progression in prodromal AD. MethodsAssociations were investigated between CSF α-synuclein and other AD biomarkers at baseline in prodromal AD stage Chinese elders. The predictive values of CSF α-synuclein in longitudinal change in clinical outcomes and conversion risk of prodromal AD stage subjects were assessed using linear mixed effects models and multivariate Cox proportional hazard models, respectively, in Alzheimer's disease Neuroimaging Initiative (ADNI) database.ResultsAmong individuals in prodromal AD stage, we detected that CSF α-synuclein levels correlated with AD-specific biomarkers CSF total tau and phosphorylated tau levels in 651 Chinese Han participants (training set). These positive correlations were replicated in ADNI database (validation set). Using a longitudinal cohort from ADNI, CSF α-synuclein concentrations increased with disease severity. CSF α-synuclein had high diagnostic accuracy for AD based on the “ATN” system (A+T+) vs controls (A-T-) (area under the receiver operating characteristic curve, 0.84). Moreover, CSF α-synuclein predicted longitudinal hippocampus atrophy and conversion from MCI to AD dementia.ConclusionsCSF α-synuclein is associated with CSF tau levels and could predict neurodegeneration and clinical progression in prodromal AD. This finding indicates CSF α-synuclein is a potentially useful, early biomarker for AD.

Standardization of hippocampus volumetry using automated brain structure volumetry tool for an initial Alzheimer’s disease imaging biomarker

2018 ◽  
Vol 60 (6) ◽  
pp. 769-776 ◽  
Author(s):  
Jill Abrigo ◽  
Lin Shi ◽  
Yishan Luo ◽  
Qianyun Chen ◽  
Winnie Chiu Wing Chu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Intraclass Correlation ◽  
Area Under The Curve ◽  
Imaging Biomarker ◽  
Imaging Biomarkers ◽  
Dice Similarity Coefficient ◽  
Reference Dataset ◽  
Magnetic Resonance Imaging Mri ◽  
Hippocampus Segmentation

Background One significant barrier to incorporate Alzheimer’s disease (AD) imaging biomarkers into diagnostic criteria is the lack of standardized methods for biomarker quantification. The European Alzheimer’s Disease Consortium-Alzheimer’s Disease Neuroimaging Initiative (EADC-ADNI) Harmonization Protocol project provides the most authoritative guideline for hippocampal definition and has produced a manually segmented reference dataset for validation of automated methods. Purpose To validate automated hippocampal volumetry using AccuBrain™, against the EADC-ADNI dataset, and assess its diagnostic performance for differentiating AD and normal aging in an independent cohort. Material and Methods The EADC-ADNI reference dataset comprise of manually segmented hippocampal labels from 135 volumetric T1-weighted scans from various scanners. Dice similarity coefficient (DSC), intraclass correlation coefficient (ICC), and Pearson’s r were obtained for AccuBrain™ and FreeSurfer. The magnetic resonance imaging (MRI) of a separate cohort of 299 individuals (150 normal controls, 149 with AD) were obtained from the ADNI database and processed with AccuBrain™ to assess its diagnostic accuracy. Area under the curve (AUC) for total hippocampal volumes (HV) and hippocampal fraction (HF) were determined. Results Compared with EADC-ADNI dataset ground truths, AccuBrain™ had a mean DSC of 0.89/0.89/0.89, ICC of 0.94/0.96/0.95, and r of 0.95/0.96/0.95 for right/left/total HV. AccuBrain™ HV and HF had AUC of 0.76 and 0.80, respectively. Thresholds of ≤ 5.71 mL and ≤ 0.38% afforded 80% sensitivity for AD detection. Conclusion AccuBrain™ provides accurate automated hippocampus segmentation in accordance with the EADC-ADNI standard, with great potential value in assisting clinical diagnosis of AD.

Association of Androgens and Gonadotropins with Amnestic Mild Cognitive Impairment and Probable Alzheimer’s Disease in Chinese Elderly Men

2020 ◽  
Vol 78 (1) ◽  
pp. 277-290
Author(s):  
Yan Li ◽  
Sha Li ◽  
Shunjiang Xu ◽  
Hong Yu ◽  
Longmei Tang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Area Under The Curve ◽  
Amnestic Mild Cognitive Impairment ◽  
Elderly Men ◽  
Age Related ◽  
Potential Biomarker ◽  
Amci Group

Background: Age-related hormone changes play important roles in cognitive decline in older men, and apolipoprotein E ɛ4 (APOE ɛ4) is a risk factor for Alzheimer’s disease (AD). Objective: This study aimed to investigate the interactive role of androgen decline and APOE ɛ4 genotype in the pathogenesis of amnestic mild cognitive impairment (aMCI) and AD. Methods: In total, 576 elderly men over 65 years old from communities in Shijiazhuang were enrolled in this study, including 243 with normal cognition (NC), 271 with aMCI, and 62 with probable AD. Cognitive function was evaluated with a battery of neuropsychological tests. The serum levels of androgen and gonadotropin were detected by ELISA and chemiluminescence immunoassay. Results: The levels of free testosterone (FT) and dihydrotestosterone (DHT) were lower in the aMCI group (p < 0.05), and even lower in the AD group (p < 0.001), but the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) were higher in AD group (p < 0.01), comparing with that in NC or aMCI group. The interaction of lower FT or DHT levels with APOE ɛ4 had a risk role in global cognitive impairment (p < 0.05). The area under the curve (AUC) of the ROC curve for predicting aMCI by serum FT levels was 0.745. Conclusion: These results indicated that the interaction of androgen decline and APOE ɛ4 genotype play a role in aMCI and AD. Serum FT levels have a predictive value for aMCI and might be a potential biomarker for prodromal AD.

Insomnia Moderates the Relationship Between Amyloid-β and Cognitive Decline in Late-Life Adults without Dementia

2021 ◽  
pp. 1-10
Author(s):  
Wei Xu ◽  
Chen-Chen Tan ◽  
Juan-Juan Zou ◽  
Xi-Peng Cao ◽  
Lan Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Amyloid Β ◽  
Cognitive Disorders ◽  
Linear Mixed Effects ◽  
Positron Emission ◽  
Prodromal Ad ◽  
Neuropsychological Evaluations ◽  
The Relationship

Background: It is suggested that not all individuals with elevated Aβ will develop dementia or cognitive impairment. Environment or lifestyle might modulate the association of amyloid pathology with cognition. Insomnia is a risk factor of cognitive disorders including Alzheimer’s disease. Objective: To investigate if insomnia moderated the relationship between amyloid-β (Aβ) and longitudinal cognitive performance in non-demented elders. Methods: A total of 385 Alzheimer’s Disease Neuroimaging Initiative participants (mean age = 73 years, 48% females) who completed 4 + neuropsychological evaluations and a [18F] florbetapir positron emission tomography scan were followed up to 8 years. Linear mixed-effects regression models were used to examine the interactions effect between insomnia and Aβ on longitudinal cognitive sores, including four domains (memory [MEM], executive function [EF], language [LAN], and visuospatial function [VS]). Results: The Aβ-positive status (A+) but not insomnia independently predicted faster cognitive decline in all domains. Furthermore, the relationship between Aβ and cognitive decline was moderated by insomnia (MEM: χ 2 = 4.05, p = 0.044, EF: χ 2 = 4.38, p = 0.036, LAN: χ 2 = 4.56, p = 0.033, and VS: χ 2 = 4.12, p = 0.042). Individuals with both elevated Aβ and insomnia experienced faster cognitive decline than those with only elevated Aβ or insomnia. Conclusion: These data reinforced the values of insomnia management in preventing dementia, possibly by interacting Aβ metabolism. Future efforts are warranted to determine whether sleep improvement will postpone the onset of dementia, specifically among populations in stages of preclinical or prodromal AD.

scholarly journals Associations between different tau-PET patterns and longitudinal atrophy in the Alzheimer's disease continuum

2021 ◽  
Author(s):  
Rosaleena Mohanty ◽  
Daniel Ferreira ◽  
Agneta Nordberg ◽  
Eric Westman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Structural Mri ◽  
Tau Pathology ◽  
Discrete Subgroups ◽  
Cognitively Normal ◽  
Prodromal Ad ◽  
Tau Pet ◽  
The Relationship

INTRODUCTION: Different subtypes/patterns have been defined using tau-PET and structural-MRI in Alzheimer's disease (AD), but the relationship between tau pathology and atrophy remains unclear. Our goals were twofold: (a) investigate the association between baseline tau-PET patterns and longitudinal atrophy in the AD continuum; (b) characterize heterogeneity as a continuous phenomenon over the conventional notion using discrete subgroups. METHODS: In 366 individuals (amyloid-beta-positive: cognitively normal, prodromal AD, AD dementia; amyloid-beta-negative healthy), we examined the association between tau-PET patterns (operationalized as a continuous phenomenon and a discrete phenomenon) and longitudinal sMRI. RESULTS: We observed a differential association between tau-PET patterns and longitudinal atrophy. Heterogeneity, measured continuously, may offer an alternative characterization, sharing correspondence with the conventional subgrouping. DISCUSSION: Site and the rate of atrophy are modulated differentially by tau-PET patterns in the AD continuum. We postulate that heterogeneity be treated as a continuous phenomenon for greater sensitivity over the current/conventional discrete subgrouping.

Sign in / Sign up

Export Citation Format

Share Document