scholarly journals Diagnostic Fluid Biomarkers in Alzheimer’s Disease: Blood and Cerebrospinal Fluid

2021 ◽  
Author(s):  
Jung Eun Park ◽  
Tamil Iniyan Gunasekaran ◽  
Yeong Hee Cho ◽  
Seong-Min Choi ◽  
Min-Kyung Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Disease Progression ◽  
Early Stage ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Preclinical Ad ◽  
T Tau

Abstract Background: Potential biomarkers for Alzheimer’s disease (AD) include amyloid β1-42 (Aβ1-42), t-Tau, p-Tau 181 , neurofilament light chain (NFL), and neuroimaging, but the feasibility of using these for the diagnosis and monitoring of AD has not been reported. Therefore, further development of these biomarkers is essential.Methods: We measured NFL and Aβ1-42 concentrations in CSF and plasma samples from 136 participants and performed correlation analysis to evaluate the utility of these biomarkers for early diagnosis and monitoring of disease progression in AD spectrum.Results: With disease progression, concentrations of NFL increased, and those of Aβ1-42 were decreases. The plasma and CSF values of NFL/Aβ1-42 were strongly correlated (r = 0.558). In addition, the plasma value of NFL/Aβ1-42 was strong correlated with hippocampal volume/ICV ( r = 0.409). In the early stage of AD, the plasma_NFL/Aβ1-42 was associated with higher diagnostic accuracy than were the individual biomarkers. Moreover, in preclinical AD, plasma_NFL/Aβ1-42 changed more rapidly than did either the t-Tau or the p-Tau181 values measured in the CSF.Conclusions: Taken together, our findings highlight the utility of plasma_NFL/Aβ1-42 as a biomarker for early diagnosis and monitoring of disease progression in AD spectrum.

scholarly journals Diagnostic Fluid Biomarkers in Alzheimer’s Disease: Blood and Cerebrospinal Fluid

2021 ◽  
Author(s):  
Jung Eun Park ◽  
Tamil Iniyan Gunasekaran ◽  
Yeong Hee Cho ◽  
Seong-Min Choi ◽  
Min-Kyung Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Disease Progression ◽  
Early Stage ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Preclinical Ad ◽  
T Tau

Abstract Background: Potential biomarkers for Alzheimer’s disease (AD) include amyloid β 1-42 (Aβ 1-42 ), t-Tau, p-Tau 181 , neurofilament light chain (NFL), and neuroimaging, but the feasibility of using these for the diagnosis and monitoring of AD has not been reported. Therefore, further development of these biomarkers is essential. Methods: We measured NFL and Aβ 1-42 concentrations in CSF and plasma samples from 136 participants and performed correlation analysis to evaluate the utility of these biomarkers for early diagnosis and monitoring of disease progression in AD spectrum. Results: With disease progression, concentrations of NFL increased, and those of Aβ 1-42 were decreases. The plasma and CSF values of NFL/Aβ 1-42 were strongly correlated ( r = 0.558). In addition, the plasma value of NFL/Aβ 1-42 was strong correlated with hippocampal volume/ICV ( r = 0.409). In the early stage of AD, the plasma_NFL/Aβ 1-42 was associated with higher diagnostic accuracy than were the individual biomarkers. Moreover, in preclinical AD, plasma_NFL/Aβ 1-42 changed more rapidly than did either the t-Tau or the p-Tau 181 values measured in the CSF. Conclusions: Taken together, our findings highlight the utility of plasma_NFL/Aβ 1-42 as a biomarker for early diagnosis and monitoring of disease progression in AD spectrum.

scholarly journals Diagnostic Blood Biomarkers in Alzheimer’s Disease

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 169
Author(s):  
Jung Eun Park ◽  
Tamil Iniyan Gunasekaran ◽  
Yeong Hee Cho ◽  
Seong-Min Choi ◽  
Min-Kyung Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Correlation Analysis ◽  
Disease Progression ◽  
Intracranial Volume ◽  
Strongly Correlated ◽  
Neurofilament Light Chain ◽  
Preclinical Ad ◽  
T Tau

Potential biomarkers for Alzheimer’s disease (AD) include amyloid β1–42 (Aβ1–42), t-Tau, p-Tau181, neurofilament light chain (NFL), and neuroimaging biomarkers. Their combined use is useful for diagnosing and monitoring the progress of AD. Therefore, further development of a combination of these biomarkers is essential. We investigated whether plasma NFL/Aβ1–42 can serve as a plasma-based primary screening biomarker reflecting brain neurodegeneration and amyloid pathology in AD for monitoring disease progression and early diagnosis. We measured the NFL and Aβ1–42 concentrations in the CSF and plasma samples and performed correlation analysis to evaluate the utility of these biomarkers in the early diagnosis and monitoring of AD spectrum disease progression. Pearson’s correlation analysis was used to analyse the associations between the fluid biomarkers and neuroimaging data. The study included 136 participants, classified into five groups: 28 cognitively normal individuals, 23 patients with preclinical AD, 22 amyloid-negative patients with amnestic mild cognitive impairment, 32 patients with prodromal AD, and 31 patients with AD dementia. With disease progression, the NFL concentrations increased and Aβ1–42 concentrations decreased. The plasma and CSF NFL/Aβ1–42 were strongly correlated (r = 0.558). Plasma NFL/Aβ1–42 was strongly correlated with hippocampal volume/intracranial volume (r = 0.409). In early AD, plasma NFL/Aβ1–42 was associated with higher diagnostic accuracy than the individual biomarkers. Moreover, in preclinical AD, plasma NFL/Aβ1–42 changed more rapidly than the CSF t-Tau or p-Tau181 concentrations. Our findings highlight the utility of plasma NFL/Aβ1–42 as a non-invasive plasma-based biomarker for early diagnosis and monitoring of AD spectrum disease progression.

scholarly journals Performance of Plasma Amyloid β, Total Tau and Neurofilament Light Chain Levels for Alzheimer’s Disease Identification

2020 ◽  
Author(s):  
Bin Jiao ◽  
Hui Liu ◽  
Lina Guo ◽  
Xinxin Liao ◽  
Yafang Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Light Chain ◽  
Amyloid Β ◽  
Amyloid Pet ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Plasma Biomarkers ◽  
Total Tau ◽  
T Tau

Abstract BackgroundRobust studies have focused on blood-based biomarkers for diagnosis of Alzheimer’s disease (AD), while the results were still controversary and failed verified in different cohorts. The aim of this study was to detect the levels of plasma amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL) in patients with AD and cognitive normal (CN) subjects, and clarify their associations with Aβ, t-tau, and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) as well as brain amyloid PET, and calculate the diagnostic efficiency of these characteristics regarding AD.Methods Plasma Aβ42, Aβ40, t-tau and NfL levels were detected by single-molecule array (Simoa) in 379 AD patients and 153 CN subjects. Additionally, lumbar puncture was conducted in 125 AD patients to detect Aβ42, Aβ40, t-tau, and p-tau levels. Brain amyloid PET was performed in 52 AD patients to identify brain amyloid deposition levels. Correlation analysis were performed between plasma biomarkers and typical biomarkers of AD, including CSF core biomarkers and amyloid PET burden. Finally, the diagnostic value of plasma biomarkers was further assessed by receiver operating characteristic (ROC) curve.ResultsCompared with the CN group, plasma Aβ42 and Aβ42/Aβ40 levels were significantly lower in AD patients, while Aβ40, t-tau and NfL levels were higher in AD patients. Among the AD patients, plasma Aβ42 was positively correlated with CSF Aβ42 (r = 0.195, p = 0.03) and Aβ42/Aβ40 (r = 0.208, p = 0.04). Moreover, plasma NfL was positively correlated with age, disease course and severity. The diagnostic model with combined plasma Aβ42, t-tau, and NfL levels controlled for age and APOE genotype showed the best performance to identify AD (area under the curve (AUC) = 0.88, sensitivity = 82.84%, specificity = 81.69%, cutoff value = 0.64).ConclusionsTrends revealed by core biomarkers were generally consistent in AD patients’ plasma and CSF. Combining plasma biomarkers can provide comparatively high AD diagnostic performance.

scholarly journals Performance of Plasma Amyloid β, Total Tau, and Neurofilament Light Chain in the Identification of Probable Alzheimer's Disease in South China

2021 ◽  
Vol 13 ◽  
Author(s):  
Bin Jiao ◽  
Hui Liu ◽  
Lina Guo ◽  
Xinxin Liao ◽  
Yafang Zhou ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Correlation Analysis ◽  
Light Chain ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Plasma Biomarkers ◽  
Total Tau ◽  
T Tau

Background: Alzheimer's disease (AD) is the most common type of dementia and has no effective treatment to date. It is essential to develop a minimally invasive blood-based biomarker as a tool for screening the general population, but the efficacy remains controversial. This cross-sectional study aimed to evaluate the ability of plasma biomarkers, including amyloid β (Aβ), total tau (t-tau), and neurofilament light chain (NfL), to detect probable AD in the South Chinese population.Methods: A total of 277 patients with a clinical diagnosis of probable AD and 153 healthy controls with normal cognitive function (CN) were enrolled in this study. The levels of plasma Aβ42, Aβ40, t-tau, and NfL were detected using ultra-sensitive immune-based assays (SIMOA). Lumbar puncture was conducted in 89 patients with AD to detect Aβ42, Aβ40, t-tau, and phosphorylated (p)-tau levels in the cerebrospinal fluid (CSF) and to evaluate the consistency between plasma and CSF biomarkers through correlation analysis. Finally, the diagnostic value of plasma biomarkers was further assessed by constructing a receiver operating characteristic (ROC) curve.Results: After adjusting for age, sex, and the apolipoprotein E (APOE) alleles, compared to the CN group, the plasma t-tau, and NfL were significantly increased in the AD group (p < 0.01, Bonferroni correction). Correlation analysis showed that only the plasma t-tau level was positively correlated with the CSF t-tau levels (r = 0.319, p = 0.003). The diagnostic model combining plasma t-tau and NfL levels, and age, sex, and APOE alleles, showed the best performance for the identification of probable AD [area under the curve (AUC) = 0.89, sensitivity = 82.31%, specificity = 83.66%].Conclusion: Blood biomarkers can effectively distinguish patients with probable AD from controls and may be a non-invasive and efficient method for AD pre-screening.

scholarly journals Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Hu ◽  
Lan Tan ◽  
Yan-Lin Bi ◽  
Wei Xu ◽  
Lin Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Late Onset ◽  
Early Stage ◽  
Susceptibility Gene ◽  
Subjective Cognitive Decline ◽  
Preclinical Ad ◽  
T Tau ◽  
New Evidence

AbstractThe bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

scholarly journals Plasma tau and neurofilament light in frontotemporal lobar degeneration and Alzheimer's disease

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011226
Author(s):  
Ignacio Illán-Gala ◽  
Alberto Lleo ◽  
Anna Karydas ◽  
Adam M. Staffaroni ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Severity ◽  
Cortical Thickness ◽  
Frontotemporal Lobar Degeneration ◽  
Amyloid Pet ◽  
Class Iii ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
T Tau

ObjectiveTo test the hypothesis that plasma total tau (t-tau) and neurofilament light chain (NfL) concentrations may have a differential role in the study of frontotemporal lobar degeneration syndromes (FTLD-S) and clinically-diagnosed Alzheimer's disease (AD-S), we determined their diagnostic and prognostic value in FTLD-S and AD-S and their sensitivity to pathologic diagnoses.MethodsWe measured plasma t-tau and NfL with the Simoa platform in 265 participants: 167 FTLD-S, 43 AD-S, and 55 healthy controls (HC), including 82 pathology-proven cases (50 FTLD-Tau, 18 FTLD-TDP, 2 FTLD-FUS, and 12 AD) and 98 participants with amyloid PET. We compared cross-sectional and longitudinal biomarker concentrations between groups, their correlation with clinical measures of disease severity, progression and survival and cortical thickness.ResultsPlasma NfL, but not plasma t-tau discriminated FTLD-S from HC and AD-S from HC. Both plasma NfL and t-tau were poor discriminators between FLTD-S and AD-S. In pathology confirmed cases, plasma NfL was higher in FTLD than AD and in FTLD-TDP compared to FTLD-Tau, after accounting for age and disease severity. Plasma NfL, but not plasma t-tau, predicted clinical decline and survival and correlated with regional cortical thickness in both FTLD-S and AD-S. The combination of plasma NfL with plasma t-tau did not outperform plasma NfL alone.ConclusionsPlasma NfL is superior to plasma t-tau for the diagnosis and prediction of clinical progression of FTLD-S and AD-S.Classification of evidenceThis study provides Class III evidence that plasma NfL has superior diagnostic and prognostic performance than plasma t-tau in FTLD and AD.

scholarly journals Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer’s disease

Brain ◽  
2020 ◽  
Author(s):  
Joana B Pereira ◽  
Shorena Janelidze ◽  
Rik Ossenkoppele ◽  
Hlin Kvartsberg ◽  
Ann Brinkmalm ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Light Chain ◽  
Diffusion Tensor ◽  
Amyloid Β ◽  
Synaptic Function ◽  
Dependent Manner ◽  
Tau Pathology ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Abstract It is currently unclear how amyloid-β and tau deposition are linked to changes in synaptic function and axonal structure over the course of Alzheimer’s disease. Here, we assessed these relationships by measuring presynaptic (synaptosomal-associated protein 25, SNAP25; growth-associated protein 43, GAP43), postsynaptic (neurogranin, NRGN) and axonal (neurofilament light chain) markers in the CSF of individuals with varying levels of amyloid-β and tau pathology based on 18F-flutemetamol PET and 18F-flortaucipir PET. In addition, we explored the relationships between synaptic and axonal markers with cognition as well as functional and anatomical brain connectivity markers derived from resting-state functional MRI and diffusion tensor imaging. We found that the presynaptic and postsynaptic markers SNAP25, GAP43 and NRGN are elevated in early Alzheimer’s disease i.e. in amyloid-β-positive individuals without evidence of tau pathology. These markers were associated with greater amyloid-β pathology, worse memory and functional changes in the default mode network. In contrast, neurofilament light chain was abnormal in later disease stages, i.e. in individuals with both amyloid-β and tau pathology, and correlated with more tau and worse global cognition. Altogether, these findings support the hypothesis that amyloid-β and tau might have differential downstream effects on synaptic and axonal function in a stage-dependent manner, with amyloid-related synaptic changes occurring first, followed by tau-related axonal degeneration.

scholarly journals Plasma tau, neurofilament light chain and amyloid-β levels and risk of dementia; a population-based cohort study

Brain ◽  
2020 ◽  
Vol 143 (4) ◽  
pp. 1220-1232 ◽  
Author(s):  
Frank de Wolf ◽  
Mohsen Ghanbari ◽  
Silvan Licher ◽  
Kevin McRae-McKee ◽  
Luuk Gras ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Plasma Levels ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Total Tau ◽  
Quartile Group ◽  
Alzheimer’S Disease Dementia

Abstract CSF biomarkers, including total-tau, neurofilament light chain (NfL) and amyloid-β, are increasingly being used to define and stage Alzheimer’s disease. These biomarkers can be measured more quickly and less invasively in plasma and may provide important information for early diagnosis of Alzheimer’s disease. We used stored plasma samples and clinical data obtained from 4444 non-demented participants in the Rotterdam study at baseline (between 2002 and 2005) and during follow-up until January 2016. Plasma concentrations of total-tau, NfL, amyloid-β40 and amyloid-β42 were measured using the Simoa NF-light® and N3PA assays. Associations between biomarker plasma levels and incident all-cause and Alzheimer’s disease dementia during follow-up were assessed using Cox proportional-hazard regression models adjusted for age, sex, education, cardiovascular risk factors and APOE ε4 status. Moreover, biomarker plasma levels and rates of change over time of participants who developed Alzheimer’s disease dementia during follow-up were compared with age and sex-matched dementia-free control subjects. During up to 14 years follow-up, 549 participants developed dementia, including 374 cases with Alzheimer’s disease dementia. A log2 higher baseline amyloid-β42 plasma level was associated with a lower risk of developing all-cause or Alzheimer’s disease dementia, adjusted hazard ratio (HR) 0.61 [95% confidence interval (CI), 0.47–0.78; P &lt; 0.0001] and 0.59 (95% CI, 0.43–0.79; P = 0.0006), respectively. Conversely, a log2 higher baseline plasma NfL level was associated with a higher risk of all-cause dementia [adjusted HR 1.59 (95% CI, 1.38–1.83); P &lt; 0.0001] or Alzheimer’s disease [adjusted HR 1.50 (95% CI, 1.26–1.78); P &lt; 0.0001]. Combining the lowest quartile group of amyloid-β42 with the highest of NfL resulted in a stronger association with all-cause dementia [adjusted HR 9.5 (95% CI, 2.3–40.4); P &lt; 0.002] and with Alzheimer’s disease [adjusted HR 15.7 (95% CI, 2.1–117.4); P &lt; 0.0001], compared to the highest quartile group of amyloid-β42 and lowest of NfL. Total-tau and amyloid-β40 levels were not associated with all-cause or Alzheimer’s disease dementia risk. Trajectory analyses of biomarkers revealed that mean NfL plasma levels increased 3.4 times faster in participants who developed Alzheimer’s disease compared to those who remained dementia-free (P &lt; 0.0001), plasma values for cases diverged from controls 9.6 years before Alzheimer’s disease diagnosis. Amyloid-β42 levels began to decrease in Alzheimer’s disease cases a few years before diagnosis, although the decline did not reach significance compared to dementia-free participants. In conclusion, our study shows that low amyloid-β42 and high NfL plasma levels are each independently and in combination strongly associated with risk of all-cause and Alzheimer’s disease dementia. These data indicate that plasma NfL and amyloid-β42 levels can be used to assess the risk of developing dementia in a non-demented population. Plasma NfL levels, although not specific, may also be useful in monitoring progression of Alzheimer’s disease dementia.

scholarly journals Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer’s Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study

2021 ◽  
Vol 10 (9) ◽  
pp. 1907
Author(s):  
James A. Hendrix ◽  
David C. Airey ◽  
Angela Britton ◽  
Anna D. Burke ◽  
George T. Capone ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
Plasma Biomarkers ◽  
Show Evidence ◽  
Biomarker Data

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

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