The discriminative capacity of CSF β-amyloid 42 and Tau in neurodegenerative diseases in the Chinese population

Ye, Lingqi; Li, Xiaoyan; Zhang, Yanbin; Cheng, Hong-Rong; Yin, Ming; Chen, Dian-Fu; Tao, Qing‐Qing; Li, Honglei; Wu, Zhi‐Ying

doi:10.1016/j.jns.2020.116756

Cited by 16 publications

(11 citation statements)

References 38 publications

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“…To the best of our knowledge, this is the first time that this panel of biomarkers commonly used in the clinic to evaluate AD cases has been explored in a large cohort of ALS patients. The larger application of these biomarkers in the clinic and their high potential to discriminate among different neurodegenerative diseases [20][21][22], combined with more sensitive techniques, should improve the early diagnosis of ALS patients. Furthermore, investigation of the levels of such proteins in the CSF of ALS patients could also improve our understanding of the pathophysiology of this disease and shed a light in other pathological mechanisms that are thus far poorly investigated, as discussed below.…”

Section: Discussionmentioning

confidence: 99%

“…The two main differences between these studies and ours is the cohort size (11, 12, and 123 ALS patients, respectively) and the disease duration-although patients in the study from Sjogren and co-authors [23] had a disease duration of 13.2 ± 4.5 years, our cohort presented a mean of 3.3 ± 2.0 years (Steinacker and co-authors [17] did not report the mean disease duration for ALS patients included in their study). Interestingly, a recent study also reported increased levels of Aβ1-42 in the CSF of ALS patients compared to controls subjects in a Chinese cohort [22]. Although not specific for ALS, some studies support a role for Aβ1-42 and amyloid precursor protein (APP) in the pathogenesis of neurodegenerative diseases than other AD, such as ALS [17,24].…”

Section: Aβ1-42 Levels and Aβ1-42/phospho-tau Ratio As Diagnosis Biommentioning

confidence: 99%

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Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis

Lanznaster

Hergesheimer

Bakkouche

et al. 2020

IJMS

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Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, but its definitive diagnosis delays around 12 months. Although the research is highly active in the biomarker field, the absence of specific biomarkers for diagnosis contributes to this long delay. Another strategy of biomarker identification based on less specific but sensitive molecules may be of interest in clinical practice. For example, markers related to other neurodegenerative diseases such as Alzheimer’s disease (AD) could be fully explored. Here, we compared baseline levels of amyloidβ1-42 (Aβ1-42), total Tau, and phosphorylated-Tau (phospho-Tau) protein in the cerebrospinal fluid (CSF) of ALS patients to controls and correlated it with clinical parameters of ALS progression collected over 12 months. We observed increased levels of Aβ1-42 (controls: 992.9 ± 358.3 ng/L; ALS: 1277.0 ± 296.6 ng/L; p < 0.0001) and increased Aβ1-42/phospho-Tau ratio and Innotest Amyloid Tau Index (IATI) (both p < 0.0001). IATI and the phospho-Tau/total Tau ratio correlated positively with ALSFRS-R and weight at baseline. Multivariate analysis revealed that baseline ALSFRS-R was associated with Aβ1-42 and phospho-Tau/total Tau ratio (p = 0.0109 and p = 0.0013, respectively). Total Tau and phospho-Tau levels correlated negatively with ALSFRS-R variation at months 6 and 9, respectively (p = 0.02 and p = 0.04, respectively). Phospho-Tau/total Tau ratio correlated positively with ALSFRS-R variation at month 9 (p = 0.04). CSF levels of Aβ1-42 could be used as a complementary tool to ALS diagnosis, and total Tau and phospho-Tau levels may help establishing the prognosis of ALS. Further studies merit exploring the pathophysiological mechanisms associated with these markers. Despite their lack of specificity, phospho-Tau/total Tau and Aβ1-42 should be combined to other biological and clinical markers in order to improve ALS management.

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Section: Discussionmentioning

confidence: 99%

Section: Aβ1-42 Levels and Aβ1-42/phospho-tau Ratio As Diagnosis Biommentioning

confidence: 99%

Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis

Lanznaster

Hergesheimer

Bakkouche

et al. 2020

IJMS

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“…The activation of the cell cycle signal transduction system was induced by cerebral ischemic injury, and cells enter into abnormal mitosis and apoptosis. This could lead to hyperphosphorylation of tau protein and formation of nerve fiber tangles, thus, participating in the pathological progress of POD ( Stadelmann et al, 1999 ; Kang et al, 2013 ; Ye et al, 2020 ). So far, no studies have proven a correlation between FHS–CVD risk score and CSF Aβ42 level ( Gupta et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

The Relationship Between Cardiovascular Disease Risk Score and Postoperative Delirium: The PNDABLE Study

Wang

Tang

et al. 2022

Front. Aging Neurosci.

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ObjectiveWe aimed to investigate the relationship between Framingham Heart Study general cardiovascular disease risk score (FHS–CVD risk score) and postoperative delirium (POD) among patients who had unilateral total knee arthroplasty performed under epidural anesthesia. Furthermore, we examined whether such a hypothesized relationship was mediated by the cerebrospinal fluid (CSF) biomarkers.MethodsA total of 750 participants were included in the current study. And the data were drawn from the database obtained from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study. The preoperative cognitive function of participants was measured by using Mini-Mental State Examination (MMSE). The incidence of POD was assessed using the Confusion Assessment Method (CAM). The POD severity was measured using the Memorial Delirium Assessment Scale (MDAS). The POD CSF biomarkers included in the current study were: Aβ42, T-tau, P-tau, Aβ42/T-tau, and Aβ42/P-tau. The level of the CSF biomarkers was measured using the enzyme-linked immune-sorbent assay (ELISA) in the PNDABLE study. Linear regression analysis was performed to examine the relationship between the FHS–CVD risk score and the POD CSF biomarkers. Logistic regression was used to analyze the relationship between FHS–CVD risk score, POD CSF biomarkers, and POD incidence. The proposed mediating effect of CSF biomarkers was evaluated using Mediation Analysis with 10,000 bootstrapped iterations. The receiver operating characteristic (ROC) curve is chosen as the evaluation metric for assessing the efficacy of the FHS–CVD risk score in predicting POD.ResultsIn the PNDABLE study, the overall incidence of POD was 22.9% with 37.2% in the higher vascular risk group and 7.9% in the lower vascular risk group. Multiple linear regression models showed that a higher preoperative FHS–CVD risk score was positively correlated with CSF T-tau (β = 0.218, P = 0.015) and P-tau level (β = 0.309, P < 0.001) in the higher vascular risk group. After adjusting for age (40–90 years), gender, education, MMSE, smoking history, drinking history, hypertension, diabetes, and the presence of CHD (cardiovascular heart disease), the results of the logistic regression analysis demonstrated the effect of Aβ42 (OR = 0.994, 95% CI 0.992–0.996, P < 0.001), Aβ42/T-tau (OR = 0.353, 95% CI 0.254–0.491, P < 0.001), and Aβ42/P-tau (OR = 0.744, 95% CI 0.684–0.809, P < 0.001) in protecting patients against POD. However, the FHS–CVD risk score (OR = 1.142, 95% CI 1.017–1.282, P = 0.025) and the remaining two biomarkers: T-tau (OR = 1.005, 95% CI 1.004–1.007, P < 0.001) and P-tau (OR = 1.045, 95%CI 1.029–1.062, P < 0.001) were identified as the risk factors. Mediation analyses revealed that the association between FHS–CVD risk score and POD was partially mediated by T-tau (proportion: 31.6%) and P-tau (proportion: 23.6%). The predictive power of the FHS–CVD risk score was validated by the ROC curve with an AUC of 0.7364.ConclusionHigher vascular risk score is one of the preoperative risk factors for POD, which is partly mediated by CSF biomarker tau protein.Clinical Trial Registration[www.clinicaltrials.gov], identifier [ChiCTR2000033439].

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“…Aβ42 has been studied in other neurodegenerative diseases involving motor neurons, such as ALS. Increased levels were reported in ALS patients with a short disease duration, 12,16 in contrast to decreased levels related to a longer disease duration or a rapidly progressive course 13,14 . It is speculated that increased levels of Aβ42 could reflect the attempt of motor neurons to survive in the early stage of the disease, whereas, in the later stage, or in rapidly progressive disease, the reduction of Aβ42 could be due to the irreversible loss of functional motor neurons.…”

Section: Discussionmentioning

confidence: 99%

Is cerebrospinal fluid amyloid‐β42 a promising biomarker of response to nusinersen in adult spinal muscular atrophy patients?

et al. 2021

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The discriminative capacity of CSF β-amyloid 42 and Tau in neurodegenerative diseases in the Chinese population

Cited by 16 publications

References 38 publications

Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis

Aβ1-42 and Tau as Potential Biomarkers for Diagnosis and Prognosis of Amyotrophic Lateral Sclerosis

The Relationship Between Cardiovascular Disease Risk Score and Postoperative Delirium: The PNDABLE Study

Is cerebrospinal fluid amyloid‐β42 a promising biomarker of response to nusinersen in adult spinal muscular atrophy patients?

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