Serum Tau Levels Research Articles

Comparison of Serum Neurofilament Light Chain and Tau Protein Levels in Cases with Autism Spectrum Disorder and Their Healthy Siblings and Healthy Controls.

: There is a growing interest among clinicians and researchers in identifying potential biomarkers associated with autism. Neurofilament light chain (NfL) and Tau protein, which are proteins associated with neurodegeneration and neuroaxonal degeneration, are particularly promising potential biomarker candidates in this field. : In this study, we compared serum NfL (sNfL) and serum Tau (sTau) levels in Autism spectrum disorder (ASD) patients, their healthy siblings (HS), and healthy controls (HC), aimed to investigate their relationship with ASD severity. Our study included 43 ASD-diagnosed participants, 43 HS participants and 42 HC participants. Clinical characteristics of the participants were assesed by Kiddie Schedule for Affective Disorders and Schizophrenia, Childhood Autism Rating Scale, Aberrant Behavior Checklist, and Strengths and Difficulties Questionnaire. Serum samples were subjected to analysis via enzyme-linked immunosorbent assay to quantitatively measure the levels of NfL and Tau protein. : sNfL levels in the ASD group were significantly higher than both of the control groups. Regarding sTau levels, no significant difference was found between study and control groups. In addition, NfL and Tau levels were not significantly correlated with ASD symptom severity. : Our findings may indicate that the sNfl levels associated with neuroaxonal damage may constitue a potential clinical biomarker rather than being an endophenotype phenomena.

Serum NFL and tau, but not serum UCHL-1 and GFAP or CSF SNAP-25, NPTX2, or sTREM2, correlate with delirium in a 3-year retrospective analysis.

Delirium represents a common terminal pathway of heterogeneous neurological conditions characterized by disturbances in consciousness and attention. Contemporary theories highlight the acute impairment of synaptic function and network connectivity, driven by neuroinflammation, oxidative stress, and neurotransmitter imbalances. However, established biomarkers are still missing. Innovative diagnostic techniques, such as single-molecule array analysis, enable the detection of biomarkers in blood at picomolar concentrations. This approach paves the way for deeper insights into delirium and potentially therapeutic targets for tailored medical treatments. In a retrospective 3-year study, we investigated seven biomarkers indicative of neuroaxonal damage [neurofilament light chain (NFL), ubiquitin carboxyl-terminal hydrolase (UCHL-1), and tau protein], microglial activation [glial fibrillary acidic protein (GFAP) and soluble triggering receptor expressed on myeloid cells 2 (sTREM2)], and synaptic dysfunction [synaptosomal-associated protein 25 (SNAP-25) and neuronal pentraxin 2 (NPTX2)]. The analysis of 71 patients with delirium, Alzheimer's disease (AD), and non-AD controls revealed that serum NFL levels are higher in delirium cases compared to both AD and non-AD. This suggests that elevated NFL levels in delirium are not exclusively the result of dementia-related damage. Serum tau levels were also elevated in delirium cases compared to controls. Conversely, cerebrospinal fluid (CSF) SNAP-25 showed higher levels in AD patients compared to controls only. These findings add to the increasing body of evidence suggesting that serum NFL could be a valuable biomarker of neuroaxonal damage in delirium research. Although SNAP-25 and NPTX2 did not exhibit significant differences in delirium, the exploration of synaptic biomarkers remains promising for enhancing our understanding of this condition.

Serum Biomarker Profiles Discriminate AQP4 Seropositive and Double Seronegative Neuromyelitis Optica Spectrum Disorder.

Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) serum levels are useful to define disease activity in different neurologic conditions. These biomarkers are increased in patients with aquaporin-4 antibody-positive NMOSD (AQP4+NMOSD) during clinical attacks suggesting a concomitant axonal and glial damage. However, there are contradictory results in double seronegative NMOSD (DS-NMOSD). The aim of this study was to characterize the neuronal, axonal, and glial damage of DS-NMOSD in comparison with AQP4+NMOSD. Patients with DS-NMOSD (i.e., for AQP4 and myelin oligodendrocyte glycoprotein antibodies-MOG-Abs) and age-matched AQP4+NMOSD diagnosed according to the latest diagnostic criteria and with available serum samples obtained within 3 months from onset/relapse were retrospectively enrolled from 14 international centers. Clinical and radiologic data were collected. Serum NfL, GFAP, tau, and UCH-L1 levels were determined using an ultrasensitive paramagnetic bead-based ELISA (SIMOA). Statistical analysis was performed using nonparametric tests and receiver-operating characteristic (ROC) curve analysis. We included 25 patients with AQP4+NMOSD and 26 with DS-NMOSD. The median age at disease onset (p = 0.611) and female sex predominance (p = 0.072) were similar in the 2 groups. The most common syndromes at sampling in both AQP4+NMOSD and DS-NMOSD were myelitis (56% vs 38.5%) and optic neuritis (34.6% vs 32%), with no statistical differences (p = 0.716). Median EDSS at sampling was 3.2 (interquartile range [IQR] 2-7.7) in the AQP4+NMOSD group and 4 (IQR [3-6]) in the DS-NMOSD group (p = 0.974). Serum GFAP, tau, and UCH-L1 levels were higher in patients with AQP4+NMOSD compared with those with DS-NMOSD (median 308.3 vs 103.4 pg/mL p = 0.001; median 1.2 vs 0.5 pg/mL, p = 0.001; and median 61.4 vs 35 pg/mL, p = 0.006, respectively). The ROC curve analysis showed that GFAP, tau, and UCH-L1, but not NfL, values were able to discriminate between AQP4+ and DS-NMOSD (area under the curve (AUC) tau: 0.782, p = 0.001, AUC GFAP: 0.762, p = 0.001, AUC UCH-L1: 0.723, p = 0.006). NfL levels were associated with EDSS at nadir only in patients with AQP4+NMOSD. Serum GFAP, tau, and UCH-L1 levels discriminate between AQP4+NMOSD and DS-NMOSD. The different biomarker profile of AQP4+NMOSD vs DS-NMOSD suggests heterogeneity of diseases within the latter category and provides useful data to improve our understanding of this disease.

Profile of serum biomarkers in seronegative NMOSD (S50.009)

Profile of serum biomarkers in seronegative NMOSD (S50.009)

APOE Is Associated With Serum Tau Following Uncomplicated Mild Traumatic Brain Injury.

Background and ObjectivesAPOE e4 has been linked to poor outcome following traumatic brain injury (TBI); however, the mechanisms behind this relationship are unclear. Few studies have investigated the relationship between the APOE genotype and established brain related protein biomarkers following TBI. The purpose of this study was to examine this relationship in service members and veterans (SMVs) following TBI.MethodsParticipants were 209 SMVs [124 uncomplicated mild TBI (mTBI); 85 complicated mild, moderate, severe, or penetrating TBI (mod-sev TBI)] prospectively enrolled in the DVBIC-TBICoE 15-Year Longitudinal TBI Study. APOE genotyping was undertaken using non-fasting blood serum samples. Participants were divided into three groups: APOE e2+, APOE e3/e3, and APOE e4+.ResultsIn participants with mTBI, those with the APOE e2 allele had significantly lower levels of tau than those with APOE e4 (p = 0.005, r = 0.43, medium-large effect size). Those with APOE e3/e3 trended toward having higher tau than those APOE e2+ (p = 0.076, r = 0.20, small-medium effect size) and lower tau than those with APOE e4+ (p = 0.062, r = 0.21, small-medium effect size). There were no significant differences in biomarkers based on APOE in the mod-sev TBI group.DiscussionThis study is the first to demonstrate APOE genotype is related to serum tau levels following a mTBI, extending prior findings to human serum following mTBI. In addition to higher serum tau levels in APOE e4 carriers, lower tau levels were observed in APOE e2 carriers, suggesting a possible protective effect.

Elevated Axonal Protein Markers Following Repetitive Blast Exposure in Military Personnel.

Blast exposures that occur during training are common in military personnel; however, the biomarkers that relate to these subtle injuries is not well understood. Therefore, the purpose of this study is to identify the acute biomarkers related to blast injury in a cohort of military personnel exposure to blast-related training. Thirty-four military personnel who participated in the training program were included in this study. Blood samples were collected before and after repetitive blast-related training on days 2 (n = 19) and days 7 (n = 15). Serum concentration (pg/mL) of tau, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau181 (p-tau181) were measured using an ultrasensitive immunoassay platform. We observed that serum p-tau181 concentrations were elevated after exposed to repetitive blast on days 2 (z = −2.983, p = 0.003) and days 7 (z = −2.158, p = 0.031). Serum tau (z = −2.272, p = 0.023) and NfL (z = −2.158, p = 0.031) levels were significantly elevated after exposure to repetitive blasts on days 7. Our findings indicate that blast exposure affects serum biomarkers indicating axonal injury.

The Early Prognostic Value and Optimal Time of Measuring Serum and Cerebrospinal Fluid Tau Protein for Neurologic Outcomes in Postcardiac Arrest Patients Treated with Targeted Temperature Management.

Neuroprognostication of cardiac arrest patients remains a challenge. We evaluated the early prognostic value and optimal time of measuring serum and cerebrospinal fluid (CSF) tau protein levels to predict neurologic outcome in postcardiac arrest patients treated with targeted temperature management (TTM). We also evaluated the cutoff values in predicting poor outcomes. Patients treated with TTM following cardiac arrest, from May 2018 to June 2019, were included in the study. Serum and CSF tau levels were obtained and compared immediately, at 24, 48, and 72 hours after return of spontaneous circulation (ROSC). The area under the receiver-operating characteristic curve (AUROC) and the Delong method were used to identify the cutoff values of serum and CSF tau protein levels in predicting poor outcomes at each interval. Of 38 patients enrolled, 16 experienced poor outcomes. Both serum and CSF tau levels were consistently higher in the poor outcome group than in the good outcome group. The AUROCs of serum and CSF tau protein were not significantly different at each time point. Immediately after ROSC, sensitivities of both serum and CSF tau protein levels were 31.25% at 100% specificity and increased to 86.6% and 73.3%, respectively, at 72 hours. This study demonstrates that serum and CSF tau protein levels could be used as valuable predictors of neurologic outcomes in postcardiac arrest patients treated with TTM. The early optimal time for measuring the serum and CSF tau protein levels was determined to be 72 hours after ROSC.

White Matter Tract Neuroimaging and Serum Biomarker Analysis in Sports-related Concussion

Background: 
 Traumatic brain injury (TBI) is a leading cause of death and disability throughout the world, estimated to carry an annual global incidence of over 27 million cases. Mild TBI (mTBI), commonly known as concussion, is the mildest form of TBI and accounts for roughly 90% of all head injuries. Sports-related concussion (SRC) contributes significantly to this statistic with millions of athletes sustaining high-impact injuries in contact sports such as football, soccer, and lacrosse. By examining the white-matter microstructure, diffusion tensor imaging (DTI) has shown excellent capabilities for detecting pathophysiologic changes after SRC and monitoring symptom progression. Biomarkers including neurofilament light (NfL) and tau have been implicated in SRC and may provide insight into the duration of post-concussive symptoms. At this time, very few studies have been published evaluating the relationship between these serum biomarkers and alterations to DTI metrics. 
 
 Methods: 
 In the present study, we examined the association between serum biomarkers NfL and tau to further understand the relationship between these biomarkers and neuroimaging findings seen with diffusion tensor imaging (DTI) after exposure to a sports-related concussive event. 
 
 Results: 
 Serum tau levels decreased significantly at the 24-48h post-injury time point compared to 6h post-injury. Serum tau levels then elevated significantly at the asymptomatic time point in comparison to the 24-48h post-injury time point. The serum tau level was significantly associated with higher mean diffusivity (MD) in the white-matter tracts. Serum NfL had minimal associations with white matter diffusion metrics. 
 
 Conclusion and Potential Impact: 
 This research serves to better inform future investigations into the relationship between DTI metrics and serum biomarkers in the context of mTBI and SRC. This information may contribute to the development of a simple bedside serum analysis with potential to offer tremendous insight into the comprehensive brain health of patients who are being evaluated for SRC, thereby streamlining the therapeutic process and providing more accessible healthcare to patients in locations where advanced imaging techniques are not readily accessible.

Relationship of Serum Tau Levels with Cognitive Functions and Factors Affecting The Cognitive Function Decrease in Parkinson's Disease Patients

Introduction: Cognitive impairment is a non-motor symptom of Parkinson's disease (PD) which occurs as the disease progresses and affects quality of life. Many efforts have been developed in early detection of cognitive disorders, one of which is the examination of tau protein biomarkers, where the tau protein that undergoes pathological changes to form neurofibrillary tangles (NFTs) is found in Alzheimer's disease and PD and plays a role in cognitive impairment. However, the role of tau in PD is still controversial. This study aims to assess the relationship between serum tau levels and cognitive function and the factors that affect cognitive function in PD patients.
 Methods: This cross-sectional design was conducted at the RSUP DR. M Djamil Padang. During the period March to August 2020, 62 research subjects were obtained. Cognitive function examination was carried out by using the MoCA-Ina test and examination of serum tau levels using the Elisa method. The relationship between categorical variables was tested by Chi square and differences in serum tau levels in the group with and without cognitive impairment were tested with the Mann Whitney test, considered statistically significant if the p value <0.05.
 Results: With Moca Ina examination, it was found that 67.7% of patients had impaired cognitive function. The mean serum tau level was 198.004 ± 162.69 ng / L.There was a significant relationship between education level and degree of disease with cognitive function (p <0.05) and there was no difference in mean serum tau levels between groups with and without cognitive impairment.
 Conclusion: There is a significant relationship between education level and degree of disease with cognitive function and there is no difference in mean serum tau protein levels between the cognitive impaired group and the cognitive normal group.

Relationship of Serum Tau Levels with Cognitive Functions and Factors Affecting The Cognitive Function Decrease in Parkinson's Disease Patients

Introduction: Cognitive impairment is a non-motor symptom of Parkinson's disease (PD) which occurs as the disease progresses and affects quality of life. Many efforts have been developed in early detection of cognitive disorders, one of which is the examination of tau protein biomarkers, where the tau protein that undergoes pathological changes to form neurofibrillary tangles (NFTs) is found in Alzheimer's disease and PD and plays a role in cognitive impairment. However, the role of tau in PD is still controversial. This study aims to assess the relationship between serum tau levels and cognitive function and the factors that affect cognitive function in PD patients.
 Methods: This cross-sectional design was conducted at the RSUP DR. M Djamil Padang. During the period March to August 2020, 62 research subjects were obtained. Cognitive function examination was carried out by using the MoCA-Ina test and examination of serum tau levels using the Elisa method. The relationship between categorical variables was tested by Chi square and differences in serum tau levels in the group with and without cognitive impairment were tested with the Mann Whitney test, considered statistically significant if the p value <0.05.
 Results: With Moca Ina examination, it was found that 67.7% of patients had impaired cognitive function. The mean serum tau level was 198.004 ± 162.69 ng / L.There was a significant relationship between education level and degree of disease with cognitive function (p <0.05) and there was no difference in mean serum tau levels between groups with and without cognitive impairment.
 Conclusion: There is a significant relationship between education level and degree of disease with cognitive function and there is no difference in mean serum tau protein levels between the cognitive impaired group and the cognitive normal group.

Serum insulin-like growth factor-binding protein 2 levels as an indicator for disease severity in enterohemorrhagic Escherichia coli induced hemolytic uremic syndrome

Background Insulin-like growth factor-binding protein (IGFBP) 2 plays an important role in the regulation of cell adhesion, migration, growth, and apoptosis. This study aimed to investigate the clinical significance of serum IGFBP2 as a biomarker for disease activity and severity in hemolytic uremic syndrome (HUS) induced by enterohemorrhagic Escherichia coli (EHEC). Methods IGFBP2 production by human renal glomerular endothelial cells (RGECs) after exposure to Shiga toxin 2 (Stx-2) was investigated in vitro. Serum IGFBP2 levels in blood samples obtained from 22 patients with HUS and 10 healthy controls (HCs) were quantified using an enzyme-linked immunosorbent assay. The results were compared to the clinical features of HUS and serum tau and cytokine levels. Results Stx-2 induced the production of IGFBP2 in RGECs in a dose-dependent manner. Serum IGFBP2 levels were significantly higher in patients with HUS than in HCs and correlated with disease severity. Additionally, serum IGFBP2 levels were significantly higher in patients with encephalopathy than in those without encephalopathy. A serum IGFBP2 level above 3585 pg/mL was associated with a high risk of encephalopathy. Furthermore, serum IGFBP2 levels significantly correlated with serum levels of tau and inflammatory cytokines associated with the development of HUS. Conclusions Correlation of serum IGFBP2 level with disease activity in patients with HUS suggests that IGFBP2 may be considered as a possible indicator for disease activity and severity in HUS. Larger studies and additional experiments using various cells in central nervous system should elucidate the true value of IGFBP2 as a clinical diagnostic marker. Abbreviations IGFBP: insulin-like growth factor-binding protein; HUS: hemolytic uremic syndrome; EHEC: enterohemorrhagic Escherichia coli; RGECs: renal glomerular endothelial cells; STx-2: Shiga toxin 2; HCs: healthy controls; LPS: lipopolysaccharide; ROC: receiver operating characteristic; sTNFR: soluble tumor necrosis factor receptor.

Tau aggregation and increased neuroinflammation in athletes after sports-related concussions and in traumatic brain injury patients – A PET/MR study

Traumatic brain injury (TBI) and repeated sports-related concussions (rSRCs) are associated with an increased risk for neurodegeneration. Autopsy findings of selected cohorts of long-term TBI survivors and rSRC athletes reveal increased tau aggregation and a persistent neuroinflammation. To assess in vivo tau aggregation and neuroinflammation in young adult TBI and rSRC cohorts, we evaluated 9 healthy controls (mean age 26 ± 5 years; 4 males, 5 females), 12 symptomatic athletes (26 ± 7 years; 6 males, 6 females) attaining ≥3 previous SRCs, and 6 moderate-to severe TBI patients (27 ± 7 years; 4 males, 2 females) in a combined positron emission tomography (PET)/magnetic resonance (MR) scanner ≥6 months post-injury. Dual PET tracers, [18F]THK5317 for tau aggregation and [11C]PK11195 for neuroinflammation/microglial activation, were investigated on the same day. The Repeated Battery Assessment of Neurological Status (RBANS) scores, used for cognitive evaluation, were lower in both the rSRC and TBI groups (p < 0.05). Neurofilament-light (NF-L) levels were increased in plasma and cerebrospinal fluid (CSF; p < 0.05), and serum tau levels lower, in TBI although not in rSRC. In rSRC athletes, PET imaging showed increased neuroinflammation in the hippocampus and tau aggregation in the corpus callosum. In TBI patients, tau aggregation was observed in thalami, temporal white matter and midbrain; widespread neuroinflammation was found e.g. in temporal white matter, hippocampus and corpus callosum. In mixed-sex cohorts of young adult athletes with persistent post-concussion symptoms and in TBI patients, increased tau aggregation and neuroinflammation are observed at ≥6 months post-injury using PET. Studies with extended clinical follow-up, biomarker examinations and renewed PET imaging are needed to evaluate whether these findings progress to a neurodegenerative disorder or if spontaneous resolution is possible.

Elevated tau and β-amyloid in the serum of fibromyalgia patients.

Fibromyalgia (FM) is a chronic widespread pain syndrome. Although its mechanism remains relatively unknown, accelerated neurodegeneration in the brain has been reported in patients with FM. Sleep disturbance can increase the risk of neurocognitive disorders, which are associated with tau and beta-amyloid (Aβ) protein accumulation. We hypothesize neurodegeneration in patients with FM may be associated with sleep disturbance. In this case-control study, we analyzed serum tau and Aβ levels and their association with symptom profiles for patients with FM, by recruiting 22 patients with FM and 22 age-matched healthy participants. The visual analog scale, Fibromyalgia Impact Questionnaire, pressure pain threshold test, Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory-II, Beck Anxiety Inventory, and serum tau and beta-amyloid-42 (Aβ-42) levels were recorded. The Mann-Whitney test was conducted to compare questionnaire and protein level results between the groups. Pearson correlation test was conducted to investigate the correlation of questionnaire scores with tau and Aβ-42 levels in patients with FM. The significance level was set at P<.05. Serum tau and Aβ-42 levels were significantly higher in patients with FM than in controls. A positive correlation between serum tau levels and PSQI scores was observed in patients with FM (r=0.476, P=.025). We found that only sleep disturbance in patients with FM was significantly associated with higher serum tau levels among all symptom scores. We suggest sleep disturbance may play a vital role in the pathomechanism of accelerated neurodegeneration in FM.

Association Between Proteomic Blood Biomarkers and DTI/NODDI Metrics in Adolescent Football Players: A Pilot Study.

While neuroimaging and blood biomarker have been two of the most active areas of research in the neurotrauma community, these fields rarely intersect to delineate subconcussive brain injury. The aim of the study was to examine the association between diffusion MRI techniques [diffusion tensor imaging (DTI) and neurite orientation/dispersion density imaging (NODDI)] and brain-injury blood biomarker levels [tau, neurofilament-light (NfL), glial-fibrillary-acidic-protein (GFAP)] in high-school football players at their baseline, aiming to detect cumulative neuronal damage from prior seasons. Twenty-five football players were enrolled in the study. MRI measures and blood samples were obtained during preseason data collection. The whole-brain, tract-based spatial statistics was conducted for six diffusion metrics: fractional anisotropy (FA), mean diffusivity (MD), axial/radial diffusivity (AD, RD), neurite density index (NDI), and orientation dispersion index (ODI). Five players were ineligible for MRIs, and three serum samples were excluded due to hemolysis, resulting in 17 completed set of diffusion metrics and blood biomarker levels for association analysis. Our permutation-based regression model revealed that serum tau levels were significantly associated with MD and NDI in various axonal tracts; specifically, elevated serum tau levels correlated to elevated MD (p = 0.0044) and reduced NDI (p = 0.016) in the corpus callosum and surrounding white matter tracts (e.g., longitudinal fasciculus). Additionally, there was a negative association between NfL and ODI in the focal area of the longitudinal fasciculus. Our data suggest that high school football players may develop axonal microstructural abnormality in the corpus callosum and surrounding white matter tracts, such as longitudinal fasciculus. A future study is warranted to determine the longitudinal multimodal relationship in response to repetitive exposure to sports-related head impacts.

Serum levels of total human Tau associated with axonal damage among severe malaria patients in Central India

Tau is a microtubule-associated protein (MAP) that is abundant in the axonal part of neurons of the central nervous system. Previous studies among African children and Vietnamese adults suffering from cerebral malaria (CM) showed the pathological significance of measuring circulatory total Tau levels. A pilot investigation was carried out to better characterise neurological pathogenesis among severe malaria patients in Central India. Serum levels of total human Tau (pg/ml) were measured by ELISA following manufacturer guidelines among hospital admitted P. falciparum malaria patients classified with different degree of severity (mild malaria = MM, non-cerebral severe malaria = NCSM, cerebral malaria survivors = CM-S and cerebral malaria non-survivors = CM-NS) using WHO, 2000 definitions, including healthy controls (HC) enroled from the hospital's blood bank. Categorical and numerical variables were analysed by applying appropriate statistical test using Stata 11.0 software. A total of 139 subjects (14 HC, 25 MM, 29 NCSM, 44 CM-S and 27 CM-NS) were included in this preliminary investigation. Serum levels of total human Tau were detected in 0% HC, 4.0% MM, 20.7% NCSM, 43.2% CM-S and 48.2% CM-NS patients. Compared to MM, percent Tau detection was significantly higher among severe malaria patients (p = 0.001). Further, compared to NCSM,% Tau detection was significantly higher in CM-S patients (Chi2 = 3.9, p = 0.048) & CM-NS patients (Chi2 = 4.7, p = 0.030). Percent Tau detection was also significantly higher among severe malaria cases presenting with multiple complications compared to those without multiple complications (p = 0.006). ROC analysis of serum Tau levels (pg/ml) revealed a fair AUC value (0.75) to distinguish CM-NS group (but not CM-S) from NCSM group. In conclusion, serum percent detection of total human Tau is associated with axonal damage among patients with different degree of P. falciparum malaria severity in Central India.

Serum tau levels are increased in patients with hyperthyroidism

Hyperthyroidism may cause cognitive decline and increases the risk of Alzheimer's disease (AD), the major form of dementia; however, the underlying mechanism of this relationship is unclear. AD is associated with increased serum levels of tau. In this study, we investigated the relationship between serum thyroid hormones (THs) and tau. Fifty participants diagnosed with hyperthyroidism and fifty euthyroid counterparts were included and received clinical examinations. Serum concentrations of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and tau protein were assessed. The total tau protein level was significantly higher in hyperthyroidism participants than in their euthyroid counterparts. The level of circulating total tau had a significant positive association with the serum concentrations of FT3 and FT4. Total tau level was increased in the low TSH group and the serum THs decreased with the increase of age. These findings reveal that peripheral THs are associated with the serum concentration of tau, which may be involved in the pathogenesis of AD, suggesting a potential therapeutic target of AD via hyperthyroidism therapy.

Serum tau as a predictor for neurological outcome after cardiopulmonary resuscitation

AimWe evaluated serum tau protein as biomarker for poor neurological outcome over an extended observation period in patients after successful cardiopulmonary resuscitation (CPR) treated with mild therapeutic hypothermia (MTH) or normothermia (NT). MethodsThis is a retrospective analysis of a prospective observational study including 132 patients after successful CPR. Serum tau was determined in 24 h intervals for up to 168 h after CPR. Patients were treated with MTH targeting a temperature of 33 °C for 24 h or NT according to current guidelines. Neurological outcome was assessed with the Cerebral Performance Categories Scale (CPC) at hospital discharge. ResultsForty-three percent of the patients were treated with MTH. Serial serum tau levels (pg/ml) showed a peak between 72–96 h after CPR (159 (IQR 27–625). Patients with poor neurological outcome (CPC 3–5) at hospital discharge (n = 68) had significantly higher serum tau levels compared to patients with good neurological outcome at 0–24 h (164 (48–946) vs. 69 (12–224); p = 0.009), at 24–48 h (414 (124–1049) vs. 74 (0–215); p < 0.001), at 48–72 h (456 (94–1225) vs. 69 (0–215); p < 0.001) and at 72–96 h (691 (197–1173) vs. 73 (0–170); p < 0.001). At 72–96 h the AUC to predict poor neurological outcome was 0.848 (95% CI: 0.737–0.959). Serum tau levels were not significantly different between patients with MTH and NT in multivariate analysis after adjusting for clinical relevant covariates. ConclusionSerum tau showed highest values and the best prognostic discrimination of poor neurological outcome at 72–96 h after CPR. Prolonged elevation may indicate ongoing axonal damage in patients with hypoxic encephalopathy.

Serum levels of tau protein increase according to the severity of the injury in DAI rat model.

Traumatic brain injury (TBI) in the form of diffuse axonal injury (DAI) is difficult to diagnose in the early phase of the injury. Early diagnosis of DAI may provide opportunity for developing treatment and management strategies. Tau protein has been demonstrated to increase in the early phase of TBI with high diagnostic accuracy in patients with DAI. We tested the biological plausibility of tau protein using a rat DAI model by evaluating the association between serum tau levels and the severity of brain injury.DAI was induced in animals using the Marmarou model.After a survival of 60 minutes, rats were anesthetized and sacrificed after obtaining blood samples (5ml) from the heart. Eighteenratswereemployedin the present studyand were randomly subjected to sham-operated control (n=4), mild DAI (n=7), and severe DAI (n=7). Of seven severe DAI rats, two rats that had focal injury caused by skull fracture were excluded in the measurement of tau protein level. The serum levels of tau protein in the rat DAI model were found to increase significantly and consistently according to the severity of the injury.Rats with DAI showed significantly higher serum levels of tau protein compared to sham rats; the severe DAI rats had higher levels of tau than moderate DAI and sham rats (sham vs. mild, P=0.02; mild vs. severe, P=0.02). In conclusion, serum tau protein levels may be useful as a biomarker for diagnosing and estimating the severity of DAI in the early phase.

Exploring Relationships Among Peripheral Amyloid Beta, Tau, Cytokines, Cognitive Function, and Psychosomatic Symptoms in Breast Cancer Survivors.

Accelerated brain aging has been proposed to explain cancer-related cognitive impairment, but empirical evidence for this relationship is lacking. The purpose of this study was to evaluate amyloid beta (Aβ) and tau, biomarkers of neurodegeneration, in relation to cognition in breast cancer survivors (BCSs). We explored relationships among peripheral concentrations of Aβ42, Aβ-40, tau, and cytokines; cognitive function; and psychosomatic symptoms in a cohort of BCSs post-chemotherapy. This secondary analysis of a cross-sectional study was conducted with 65 BCSs. Serum total Aβ-42, Aβ-40, and tau levels were measured with single molecule array technology. Cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, granulocyte-macrophage colony-stimulating factor [GM-CSF], interferon [IFN]-g, IL-10, IL-12, IL-13, IL1-b, IL-2, IL-4, IL-5, IL-7, and IL-8) were simultaneously measured in serum using multiplex assays. Cognitive function was measured with five standardized neuropsychological tests and psychosomatic symptoms (stress, loneliness, anxiety, depressive symptoms, fatigue, sleep quality, and daytime sleepiness) with self-report questionnaires. Data analyses included correlations and random forest regression (RFR). Significant correlations were identified among hip-to-waste ratio, number of treatment modalities, Aβ-42, Aβ-40, and tau levels (rs = .27-.35, ps < .05). RFR modeling including Aβ-42, Aβ-40, tau, and cytokines as features explained significant variance in cognitive function (R2 = .71, F = 9.01, p < .0001) and psychosomatic symptoms (R2 = .74, F = 10.22, p < .0001). This study suggests that neurodegenerative biomarkers interact with cytokines to influence cognitive functioning and psychosomatic symptoms in BCSs following chemotherapy, but additional research is needed.

Abstract 1352: Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas

Abstract Introduction: While the morbidity and mortality attributable to gliomas and brain metastases is significant, there are currently no approved biomarkers for detecting and monitoring intracranial disease and imaging remains the primary modality. Blood levels of the neurofilament light (NfL) and tau, as well as glial fibrillary acidic protein (GFAp) show promise as biomarkers for brain injury. We therefore hypothesized that these biomarkers would correlate with CNS activity of gliomas and brain metastases. Methods: Serum concentrtaions of NfL, tau and GFAp were measured using the ultrasensitive single molecule array (Simoa) technology (Quanterix, Lexington, MA). Levels of the three proteins were then correlated with status of gliomas and brain metastases in the patients. Statistical analysis was performed using GraphPad Prism7 and all p-values were 2-tailed with an accepted 2-sided alpha level of 0.05 as statistically significant. Results: 36 patients were enrolled with varying malignancies. Both serum NfL and GFAp levels were significantly associated with the state of intracranial disease (ANOVA psNfL= 0.0307; ANOVA pGFAp=0.0348). In contrast, serum tau levels were discordant with brain involvement with cancer (ANOVA pTau= 0.1453). Conclusion: Serum NfL and GFAp both apparently vary closely with presence and activity of gliomas and brain metastases. Our studies are among the first to identify possible candidate serum biomarkers for screening and monitoring cancer patients for CNS involvement with malignancy. Further studies in larger populations are needed to expand these findings. Citation Format: Jason Porter, Adriana Hepner, Manjari Pandey, Philippe Prouet, Felicia Hare, Syed S. Nasir, Madison Boles, Henrik Zetterberg, Kaj Blennow, Michael Martin. Serum neurofilament light (NfL), glial fibrillary acidic protein (GFAp) and tau protein are possible serum biomarkers for activity of brain metastases and gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1352.