Serum Total Tau Research Articles

25 Associations between Diffusion Kurtosis Imaging, Tau, and Cognitive Outcomes in TBI

Objective:Determine associations between cognitive outcomes in remote TBI (i.e., at least 6 months post injury), a blood marker of neural degeneration (i.e., Tau), and diffusion kurtosis imaging (DKI) measures (e.g., mean or radial kurtosis). Because DKI imaging is sensitive to the environmental complexity of the imaged area, we sought to investigate regions known to be associated with the cognitive and emotional sequalae of TBI, such as the anterior thalamic radiations, uncinate fasciculus, and the corpus callosum.Participants and Methods:41 individuals with mild-to-moderate TBI and a mean age(SD) of 36.1(10.4) years underwent DKI, a blood draw, and neuropsychological assessments. 23 healthy controls (HC) with a mean age(SD) of 35.2(15.2) years underwent the blood draw and assessments, but no imaging. Higher diffusion kurtosis indicates more restricted diffusion, possibly due to greater complexity within the imaged region. Thus, in the context of TBI, DKI can be used as a proxy measurement for biological processes that alter the complexity of imaged environments, such as reactive gliosis. Some people show cognitive deficits long after TBI and this could be associated with increased inflammation and membrane protein aggregates in damaged brain regions. We used bivariate correlations and general linear models to investigate the association of mean kurtosis (MK) in long white matter tracts and Tau (total or phosphorylated) to color-word Stroop scores; a measure of fronto-subcortical function.Results:In patients with TBI, MK was significantly associated with serum total Tau (TTau) in the right (r=-0.396) and left (r=-0.555) uncinate fasciculus (UF), right (r=-0.402) and left (r=-0.504) anterior thalamic radiations (ATR), and the genu (r=-0.526) and body (r=-0.404) of the corpus callosum (CC). TTau had a significant association with word Stroop scores, F(1,63)=-2.546, p=0.013. However, there was no significant effect of group (i.e., TBI or HC), F(2,63)=-0.426, p=0.672, on cognitive performance. When models were implemented that included both TTau and MK in either the UF or ATR as explanatory variables to predict word Stroop scores, TTau levels and MK in the right UF explained a significant amount of the variance in Stroop performance, F(1,29)=2.215, p=0.025. Further, there was also a significant association between radial kurtosis in the right UF and Stroop word scores (r= 0.366).Conclusions:Our results show that an indicator of biological complexity (DKI) in cognitively important brain regions is associated with cognitive performance and Tau in patients with remote mild-to-moderate TBI. The UF is a critical fronto-temporal/subcortical pathway that has previously been implicated in the manifestation of executive dysfunction and mood dysregulation in TBI. Tau is an important marker of neurodegeneration implicated in Alzheimer’s disease, Parkinson’s disease, and chronic traumatic encephalopathy (CTE), and DKI is potentially sensitive to markers of neurodegeneration. The association of Tau and DKI measures is novel and shows concordance between blood and brain imaging markers and cognitive performance in patients with mild to moderate TBI.

Serum total tau, neurofilament light, and glial fibrillary acidic protein are associated with mortality in a population study.

Total tau (t-tau), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) are neuronal cytoskeletal biomarkers that may indicate greater risk of poor outcomes in age-related conditions, including mortality. Health disparities experienced by some racial minority subgroups may influence biomarker expression and effects on longevity. We aimed to examine (a) associations of serum t-tau, NfL, and GFAP with overall and cardiovascular mortality and (b) differences in associations by racial background. Data came from 1327 older participants from the Chicago Health and Aging Project (CHAP), a longitudinal population-based study. Cox proportional hazards regression models were used to examine associations between concentrations of serum t-tau, NfL, and GFAP biomarker(s) and mortality (overall/cardiovascular mortality based on age at death). Interaction terms were used to examine differences between African-American and European-American participants. Models were adjusted for age, sex, education, the APOE-ε4 allele, body mass index, chronic health conditions, and cognitive and physical functioning. Models showed that fivefold higher concentrations of t-tau (HR = 1.46, 95% CI: 1.27, 1.68), NfL (HR = 2.13, 95% CI: 1.76, 2.58), and GFAP (HR = 1.43, 95% CI: 1.08, 1.90) were separately associated with increased risk of overall mortality, with higher risk in African Americans in t-tau or NfL. In models with all biomarkers, NfL (HR = 2.17, 95% CI: 1.65, 2.85) was associated with risk of overall mortality, with racial differences in t-tau. Higher concentrations of t-tau (HR = 1.32, 95% CI: 1.02, 1.70), NfL (HR = 1.95, 95% CI: 1.40, 2.72), and GFAP (HR = 1.87, 95% CI: 1.18, 2.98) were separately associated with risk of cardiovascular mortality, with racial differences in t-tau, NfL, or GFAP. In combined models, NfL (HR = 1.73, 95% CI: 1.08, 2.78) was associated with cardiovascular mortality. Serum t-tau, NfL, and GFAP may be early indicators for mortality outcomes among older adults, with racial differences among associations.

Serum tau protein elevation in migraine: a cross-sectional case–control study

BackgroundMigraine is a disorder associated with neuropeptide release, pain and inflammation. Tau protein has recently been linked to inflammatory diseases and can be influenced by neuropeptides such as CGRP, a key neurotransmitter in migraine. Here, we report serum concentrations of total-tau protein in migraine patients and healthy controls.MethodsIn this cross-sectional study, interictal blood samples from n = 92 patients with episodic migraine (EM), n = 93 patients with chronic migraine (CM), and n = 42 healthy matched controls (HC) were studied. We assessed serum total-tau protein (t-tau) and for comparison neurofilament light chain protein (NfL), glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L (UCH-L1) concentrations using the Neurology 4-plex kit, on a single molecule array HD-X Analyzer (Quanterix Corp Lexington, MA). Matched serum/cerebrospinal fluid (CSF) samples were used for post-hoc evaluations of a central nervous system (CNS) source of relevant findings. We applied non-parametric tests to compare groups and assess correlations.ResultsSerum t-tau concentrations were elevated in EM [0.320 (0.204 to 0.466) pg/mL] and CM [0.304 (0.158 to 0.406) pg/mL] patients compared to HC [0.200 (0.114 to 0.288) pg/mL] (p = 0.002 vs. EM; p = 0.025 vs. CM). EM with aura [0.291 (0.184 to 0.486 pg/mL); p = 0.013] and EM without aura [0.332 (0.234 to 0.449) pg/mL; p = 0.008] patients had higher t-tau levels than HC but did not differ between each other. Subgroup analysis of CM with/without preventive treatment revealed elevated t-tau levels compared to HC only in the non-prevention group [0.322 (0.181 to 0.463) pg/mL; p = 0.009]. T-tau was elevated in serum (p = 0.028) but not in cerebrospinal fluid (p = 0.760). In contrast to t-tau, all proteins associated with cell damage (NfL, GFAP, and UCH-L1), did not differ between groups.DiscussionMigraine is associated with t-tau elevation in serum but not in the CSF. Our clinical study identifies t-tau as a new target for migraine research.

Astrogliosis marker 11C-SL2511.88 PET in traumatic brain injury with persistent symptoms.

Traumatic brain injury (TBI) is common but little is known why up to a third of patients have persisting symptoms. Astrogliosis, a pathophysiological response to brain injury, may be a potential therapeutic target, but demonstration of astrogliosis in the brain of humans with TBI and persistent symptoms is lacking. Astroglial marker monoamine oxidase B total distribution volume ([11C]SL25.1188 VT), an index of MAO-B density, was measured in 29 TBI and 29 similarly aged healthy control cases with [11C]SL25.1188 PET, prioritizing prefrontal cortex (PFC) and cortex proximal to cortical convexity. Correlations of PFC [11C]SL25.1188 VT with psychomotor and processing speed; and serum blood measures implicated in astrogliosis were determined. [11C]SL25.1188 VT was greater in TBI in PFC (P=0.00064) and cortex (P=0.00038). PFC [11C]SL25.1188 VT inversely correlated with Comprehensive Trail Making Test psychomotor and processing speed (r=-0.48, P=0.01). In participants scanned within two years of last TBI, PFC [11C]SL25.1188 VT correlated with serum glial fibrillary acid protein (r=0.51, P=0.037) and total tau (r=0.74, P=0.001). Elevated [11C]SL25.1188 VT argues strongly for astrogliosis and therapeutics modifying astrogliosis towards curative phenotypes should be tested in TBI with persistent symptoms. Given substantive effect size, astrogliosis PET markers should be applied to stratify cases and/or assess target engagement for putative therapeutics targeting astrogliosis.

Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study.

Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated. We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline. In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR=2.06 (1.60-2.67) and 9.22 (4.48-18.9). NfL was independently associated with accelerated cognitive decline. Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.

Serum total tau, neurofilament light, and glial fibrillary acidic protein are associated with overall and cardiovascular mortality in a biracial longitudinal population‐based cohort

AbstractBackgroundSerum cytoskeletal biomarkers may indicate greater risk of poor outcomes in age‐related conditions, including mortality. Total tau (t‐tau), neurofilament light (Nf‐L) and glial fibrillary acidic protein (GFAP) are neuronal cytoskeletal biomarkers that are measurable in biofluids. Our objective is to examine separate and combined associations of serum t‐tau, Nf‐L, and GFAP with overall and cardiovascular mortality in a biracial population‐based sample.MethodData came from 1,327 older participants who were either of Black or White racial background from the Chicago Health and Aging Project (CHAP), a longitudinal population‐based study of chronic conditions of aging. An ultrasensitive immunoassay was used to measure the concentration of t‐tau, Nf‐L, and GFAP in blood serum. Mortality based on age at death included overall mortality and cardiovascular mortality. A series of Cox proportional hazard regression models were used to examine associations between biomarker(s) and outcomes (overall and cardiovascular mortality), adjusting for age, gender, education, the APOE‐e4 allele, global cognitive function, and physical functioning.ResultIn univariate models, 5‐fold higher concentrations of serum t‐tau (HR = 1.46, 95% CI: 1.28, 1.68), Nf‐L (HR = 2.14, 95% CI: 1.79, 2.57), and GFAP (HR = 1.39, 95% CI: 1.07, 1.81) were separately associated with increased risk of overall mortality, with higher risk in participants of Black race versus White in models with t‐tau or Nf‐L. In combined models with all three biomarkers, t‐tau (HR = 1.38, 95% CI: 1.09, 1.75) and Nf‐L (HR = 3.05, 95% CI: 2.35, 3.95) were associated with risk of overall mortality, with racial differences in t‐tau only. In univariate models, higher concentrations of t‐tau (HR = 1.32, 95% CI: 1.03, 1.68), Nf‐L (HR = 2.11, 95% CI: 1.56, 2.88), and GFAP (HR = 1.74, 95% CI: 1.13, 2.69) were separately associated with risk of cardiovascular mortality, with racial differences in t‐tau or Nf‐L. In combined models, only Nf‐L was associated with cardiovascular mortality (HR = 2.84, 95% CI: 1.84, 4.38).ConclusionSerum t‐tau, Nf‐L, and GFAP were associated with increased risk of overall and cardiovascular mortality, with racial differences among associations, in a biracial population‐based sample. Our findings suggest that serum t‐tau, Nf‐L, and GFAP may serve as a potential biomarker for overall and cardiovascular mortality among older adults.

TEMPORAL ASSOCIATIONS OF SENSORY FUNCTION AND BLOOD-BASED NEURODEGENERATIVE AND ALZHEIMER'S DISEASE BIOMARKERS

Abstract Sensory changes are risk factors of neurodegeneration and Alzheimer’s Disease (AD) but their relations with emerging blood-based biomarkers of neurodegeneration and AD are rather unknown. We assessed long-term temporal relationships of sensory functions and blood-based neurodegenerative and AD biomarkers.This study is based on 10-year follow-up data of n=1529 (primarily middle-aged) Beaver Dam Offspring Study participants. We conducted pure-tone audiometry, visual acuity testing, and quantified serum neurofilament light chain (NfL), total tau, and amyloid beta. Linear mixed-effects and linear regression models were used to determine longitudinal associations and the effect sizes of temporal effects.Preliminary analyses revealed that NfL increased slightly more slowly per year with every 1SD better hearing (-0.3%/year[-0.5%,-0.1%]) and vision (-0.2%/year[-0.4%,0.01%]). Effect sizes of baseline sensory function effects on NfL levels 10-years later were 3-4 times larger than effects of the opposite direction. Longer follow-up is needed to confirm whether hearing changes occur before blood-based NfL changes.

Brain injury in COVID-19 is associated with dysregulated innate and adaptive immune responses.

COVID-19 is associated with neurological complications including stroke, delirium and encephalitis. Furthermore, a post-viral syndrome dominated by neuropsychiatric symptoms is common, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of COVID-19 severity.We investigated the dynamics of, and relationship between, serum markers of brain injury (neurofilament light [NfL], glial fibrillary acidic protein [GFAP] and total tau) and markers of dysregulated host response (autoantibody production and cytokine profiles) in 175 patients admitted with COVID-19 and 45 patients with influenza.During hospitalisation, sera from patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependent manner, with evidence of ongoing active brain injury at follow-up 4 months later. These biomarkers were associated with elevations of pro-inflammatory cytokines and the presence of autoantibodies to a large number of different antigens. Autoantibodies were commonly seen against lung surfactant proteins but also brain proteins such as myelin associated glycoprotein. Commensurate findings were seen in the influenza cohort.A distinct process characterised by elevation of serum total tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses unlike NfL and GFAP.These results demonstrate that brain injury is a common consequence of both COVID-19 and influenza, and is therefore likely to be a feature of severe viral infection more broadly. The brain injury occurs in the context of dysregulation of both innate and adaptive immune responses, with no single pathogenic mechanism clearly responsible

Blood-Based Biomarkers for Alzheimer's Disease in Older Adults with Posttraumatic Stress Disorder.

Background:Posttraumatic stress disorder (PTSD) is associated with cognitive decline and risk for dementia, but the neuropathology involved is unclear.Objective:The aim of this study was to determine whether PTSD is associated with increased levels of Alzheimer’s disease (AD) blood-based biomarkers.Methods:Individuals aged 50 years and older with PTSD were compared to trauma-exposed healthy controls (TEHCs) at baseline on serum measures of amyloid-β (Aβ) 42 and 40 levels, the Aβ42/Aβ40 ratio, and total tau. Serum was analyzed using ultrasensitive Simoa Human Neurology 3-Plex A assay (N3PA). Linear regressions modeling each AD biomarker as a function of group were used to investigate between-group differences, controlling for age, sex, and educational attainment (years).Results:TEHC participants (N = 26) were 53.8% male with mean age 66.8±10.7, whereas PTSD participants (N = 44) were 47.7% male and aged 62.5±9.1 years. No between-group differences were noted on demographic characteristics or cognitive performance measured with the NIH Toolbox Cognition Battery. There were no significant between-group differences in serum Aβ40 (TEHC 105.8±51.6 versus PTSD 93.2±56.1, p = 0.46), Aβ42 (TEHC 8.1±4.6 versus PTSD 7.8±4.6, p = 0.63), Aβ42/Aβ40 (TEHC 0.08±0.03 versus PTSD 0.09±0.03, p = 0.27), or total tau (TEHC 0.5±0.3 versus PTSD 0.5±0.4, p = 0.77). Likewise, there were no significant interaction effects of amyloid or tau serum concentrations and PTSD group status on cognitive functioning.Conclusion:Findings from cognitive assessments and serum analyses do not support PTSD-induced neurodegeneration of the Alzheimer’s type as a pathway linking PTSD to increased incidence of dementia in older adults.

Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia.

IntroductionNeurological complications among hospitalized COVID‐19 patients may be associated with elevated neurodegenerative biomarkers.MethodsAmong hospitalized COVID‐19 patients without a history of dementia (N = 251), we compared serum total tau (t‐tau), phosphorylated tau‐181 (p‐tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy‐terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in‐hospital death versus survival, and discharge home versus other dispositions. COVID‐19 patient biomarker levels were also compared to non‐COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161).ResultsAdmission t‐tau, p‐tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in‐hospital, while t‐tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non‐COVID controls with MCI or AD.DiscussionNeurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID‐19 patients.

Longitudinal evaluation of total tau and physical activity on cognitive decline in a population‐based study

AbstractBackgroundLittle is known about the longitudinal relationships of physical activity (PA) and serum total tau (tau) on cognitive decline. We examined if PA moderated the association of tau and cognitive decline in a biracial, population‐based sample of older adults.MethodWe studied 1,159 participants in the Chicago Health and Aging Project (CHAP), who provided blood and completed neuropsychological tests of episodic memory, perceptual speed, and the Mini‐Mental State Examination (MMSE). A standardized global cognitive function test score was computed using individual tests. Self‐report PA was categorized into three groups‐ No PA (responded to at least four of five specified activity items and reported no activity for all responses), low PA (< 150 minutes/week), and high PA ( > 150 minutes/week). Tau concentrations were measured by ultrasensitive immunoassay and classified as low (<0.40 pg/mL) and high (>0.40 pg/mL).ResultThe average age of study participants (63% females and 60% African Americans) was 77 years, with a mean education of 13 years. After adjusting for demographic characteristics and APOE‐ε4 allele, among participants with high tau concentrations, the rate of cognitive decline for participants with high PA (β= ‐0.047, 95% CI= ‐0.067, ‐0.027) was 70% slower than for participants with no PA (β= ‐0.080, 95% CI= ‐0.101, ‐0.058). Similar associations were observed for individual cognitive tests. Specifically, comparing participants with high PA to no PA among those with high tau concentrations, the rate of annual decline in episodic memory was slower by 92%, perceptual speed by 62%, and MMSE by 80%. Among participants with low tau concentrations, high PA (β= ‐0.035, 95% CI= ‐0.052, ‐0.019) was associated with a 77% slower cognitive decline in annual rate compared to no PA (β= ‐0.046, 95% CI= ‐0.066, ‐0.026). Individual tests of those with low tau concentrations showed the annual rate of decline in episodic memory was slower by 76%, perceptual speed by 78%, and MMSE by 68% for high versus low PA.ConclusionPA significantly slowed cognitive decline in participants with high and low concentrations of tau. These findings may inform the development of prevention trials tailored to at‐risk characteristics with long‐term follow‐up measurement.

Blood biomarkers for dementia in Hispanic and non-Hispanic White adults.

IntroductionThe study evaluated if blood markers reflecting diverse biological pathways differentiate clinical diagnostic groups among Hispanic and non‐Hispanic White adults.MethodsWithin Hispanic (n = 1193) and non‐Hispanic White (n = 650) participants, serum total tau (t‐tau), neurofilament light (NfL), ubiquitin carboxyl‐terminal hydrolase LI, glial fibrillary acidic protein (GFAP), soluble cluster of differentiation‐14, and chitinase‐3‐like protein 1 (YKL‐40) were quantified. Mixed‐effects partial proportional odds ordinal logistic regression and linear mixed‐effects models were used to evaluate the association of biomarkers with diagnostic group and cognition, adjusting for age, sex, ethnicity, apolipoprotein E ε4, education, and site.ResultsT‐tau, NfL, GFAP, and YKL‐40 discriminated between diagnostic groups (receiver operating curve: 0.647–0.873). Higher t‐tau (odds ratio [OR] = 1.671, 95% confidence interval [CI] = 1.457–1.917, P < .001), NfL (OR = 2.150, 95% CI = 1.819–2.542, P < .001), GFAP (OR = 2.283, 95% CI = 1.915–2.722, P < .001), and YKL‐40 (OR = 1.288, 95% CI = 1.125–1.475, P < .001) were associated with increased likelihood of dementia relative to cognitively unimpaired and mild cognitive impairment groups. Higher NfL was associated with poorer global cognition (β = –0.455, standard error [SE] = 0.083, P < .001), semantic fluency (β = –0.410, SE = 0.133, P = .002), attention/processing speed (β = 2.880, SE = 0.801, P < .001), and executive function (β = 5.965, SE = 2.037, P = .003). Higher GFAP was associated with poorer global cognition (β = –0.345, SE = 0.092, P = .001), learning (β = –1.426, SE = 0.359, P < .001), and memory (β = –0.890, SE = 0.266, P < .001). Higher YKL‐40 (β = –0.537, SE = 0.186, P = .004) was associated with lower memory scores. Interactions with ethnicity were observed for learning (NfL, GFAP, YKL‐40), memory (NfL, GFAP), and semantic fluency (NfL; interaction terms P < .008), which were generally no longer significant in a demographically matched subset of Hispanic and non‐Hispanic White participants.DiscussionBlood biomarkers of neuronal/axonal and glial injury differentiated between clinical diagnostic groups in a bi‐ethnic cohort of Hispanic and non‐Hispanic Whites. Our results add to the growing literature indicating that blood biomarkers may be viable tools for detecting neurodegenerative conditions and highlight the importance of validation in diverse cohorts.

Blood Biomarkers Relate to Cognitive Performance Years after Traumatic Brain Injury in Service Members and Veterans.

This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI). Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted. Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065-.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052-.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029). Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.

Serum and saliva total tau protein as a marker for relapsing-remitting multiple sclerosis

Multiple sclerosis (MS) is considered as motor and sensory function loss, which results from demyelination and following axonal lesion. Tau protein interferes in the construction and stabilization of microtubules that are needed for axonal transport. We hypothesize that the level of tau protein alters in MS, so we examined the level of total tau protein in serum, stimulated and unstimulated saliva as a suitable biomarker for detecting of relapsing-remitting MS. A case-control study was carried out in 30 healthy women and 30 who suffer MS and were hospitalized in Imam Reza hospital, Tehran, Iran. Total tau protein level was assayed in serum and stimulated and unstimulated whole saliva. Total tau protein was expressed at a lower level in serum of MS patients compared to control groups. The serum total tau protein level negatively correlated with EDSS. There was no significant difference in saliva total tau protein between MS and healthy individuals. Moreover, there was no significant correlation between saliva and serum total tau protein and between saliva total tau protein and EDSS. The serum level of tau protein is lower in MS and it may be considered as a potential biomarker in Multiple sclerosis. However, it seems that tau protein in the saliva isn’t a suitable biomarker for detection of MS.

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.

Characterisation of serum total tau following paediatric traumatic brain injury: a case-control study

Traumatic brain injury (TBI) is a major health problem in children. Blood-based biomarkers interpreted by use of normative values might improve the accuracy of diagnosis. Ultrasensitive assays can quantify serum concentrations of the neuronal microtubule-associated protein tau, which is increased in adult brains following TBI. We aimed to determine if serum total tau correlates with TBI diagnosis, severity, and radiological findings on CT scans in children younger than 18 years. In this case-control study, we included venous blood samples from healthy control children in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) biobank. For TBI cases, we recruited children (aged 0-17 years) who presented to the emergency department within 24 h of a TBI in three tertiary-care paediatric hospitals (Toronto, Vancouver, and Melbourne). Children were eligible if they required hospital observation for a minimum of 4 h or admission to the intensive care unit, and were excluded if they had had hospital treatment for a previous TBI, had birth trauma, or their parents could not speak English or French and therefore could not readily give consent. All available control samples were used and a case-control match was therefore not done. Venous and arterial blood samples were collected from patients with TBI within 28 h of injury (day 1). We used an ultrasensitive single-molecule immunoassay to measure serum total tau in blood samples. We first generated reference intervals of serum total tau from the control group, and used these normative data to interpret injury-associated changes in serum total tau in children with TBI. Concentrations of serum tau were measured in all CALIPER participants and patients with TBI, and no participants were excluded before analysis. We included samples from 416 control participants from the CALIPER cohort. Median total tau concentrations did not differ between sexes (p=0·12), but three significant reference intervals based on age groups were identified (1-3 years [0·88-19·2 pg/mL], 4-15 years [0·93-5·31 pg/mL], and 16-19 years [0·79-4·20 pg/mL]). Blood samples were obtained from 158 patients with TBI recruited between April 30, 2011, and June 28, 2013. Serum total tau on day 1 of TBI was negatively associated with Glasgow Coma Scale (GCS) score (rs=-0·42, 95% CI -0·55 to -0·28, p<0·0001). Median total tau was 2·86 pg/mL (IQR 1·52-4·83) in patients with GCS score 13-15 points (n=114), 7·08 pg/mL (3·75-41·1) in those with GCS score 9-12 points (n=13), and 8·48 pg/mL (2·53-70·6) in those with GCS score 3-8 points (n=31). Notably, participants who had GCS scores of 15 points had median total tau concentrations (2·57 pg/mL [1·50-4·61]) indistinguishable from those of control participants (2·46 pg/mL [1·77-3·42]), whereas those with GCS score 13-14 points had elevated total tau (6·41 pg/mL [2·97-42·5]). Serum total tau was not strongly associated with CT findings in patients with mild TBI. Serum total tau might help to differentiate between patients with mild TBI (GCS 13-14 vs GCS 15), but larger studies are needed to validate these results before this biomarker can be used for diagnosis and prognosis. Canadian Institutes of Health Research, Ontario Neurotrauma Foundation, and Victoria Neurotrauma Foundation.

Total Tau and Phosphorylated Tau Protein Serum Levels in Patients with Schizophrenia Compared with Controls

Tau protein is located in the axons of neurons and in Alzheimer Disease, is abnormally phosphorylated and aggregates into paired helical filaments (neurofibrillary tangles) reflecting the degree of neurofibrillary pathology and neurodegeneration. Although tau and phosphorylated tau (p-Tau) pathology is a hallmark for dementia, few studies were performed in patients of schizophrenia. This preliminary serum study was designed to compare serum total tau and p-Tau levels of schizophrenia patients with healthy controls. The study was included 42 patients diagnosed with schizophrenia and 42 healthy control subjects. Sociodemographic form was applied to both groups and PANSS was applied to patient group. Serum total tau and p-Tau levels were measured by ELISA method. Total tau and p-Tau levels of patients were significantly lower than healthy controls. There was a positive correlation between amount of past electroconvulsive therapies and total tau level. However total tau and p-Tau levels were positively correlated. Our study results showed that serum total tau and p-Tau levels of patients with schizophrenia were significantly lower than healthy controls.

Tau proteins in serum predict neurological outcome after hypoxic brain injury from cardiac arrest: Results of a pilot study

ObjectiveTo conduct a pilot study to evaluate the prognostic potential of serum tau protein measurements to predict neurological outcome 6 months following resuscitation from cardiac arrest. MethodsIn this retrospective observational study, we employed a new ultra sensitive digital immunoassay technology to examine serial serum samples from 25 cardiac arrest patients to examine tau release into serum as a result of brain hypoxia, and probe for its significance predicting six-month neurological outcome. Serial blood samples were obtained from resuscitated cardiac arrest survivors during their first five days in an intensive care unit, and serum total tau was measured. Cerebral function assessments were made using Cerebral Performance Categorization (CPC) at discharge from the ICU and six months later. Tau data were analyzed in the context of 6-month CPC scores. ResultsTau elevations ranged from modest (<10pg/mL) to very high (hundreds of pg/mL), and exhibited unexpected bi-modal kinetics in some patients. Early tau elevations appeared within 24h of cardiac arrest, and delayed elevations appeared after 24–48h. In patients with delayed elevations, areas under the curves of tau concentration vs. hours since cardiac arrest were highly predictive of 6-month outcome (P<0.0005). ConclusionHigh-sensitivity serum tau measurements combined with an understanding of tau release kinetics could have utility for hypoxic brain injury assessment and prediction of cerebral function outcome.

CSF and serum total-tau and phospho-tau(181P) in MS patients

AbstractIn search of biological marker in multiple sclerosis (MS), total-tau and phospho-tau (Thr181) concentrations were established in CSF and serum of 78 patients with MS, using commercially available kits. Serum and CSF concentrations of IgG, IgM, and albumin were assayed simultaneously to calculate quotients and indices of intrathecal synthesis. Serum t-tau detection was strikingly low (23.1%); therefore, this factor was excluded from further analysis. Serum p-tau levels did not correlate with any of indices or quotients. Unexpectedly, CSF t-tau and p-tau showed an inverse relation with MSSS and EDSS, which has not been published elsewhere. Our results do not support utility of serum t-tau and p-tau as surrogate markers for MS.

Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury

We investigated if tau, microtubular binding protein, in serum and ventricular CSF (vCSF) in patients with severe traumatic brain injury (TBI) during the initial posttraumatic days correlated to 1-year outcome. Patients with severe TBI (n = 39, Glasgow Coma Scale score <or=8) were included. We measured serum and vCSF total tau on days 0 to 14, using ELISA. vCSF total tau correlated to 1-year Extended Glasgow Outcome Scale (GOSE), the NIH Stroke Scale (NIHSS) neurologic status, and the Bartel Daily Living Index. Patients (n = 20) with normal pressure hydrocephalus (NPH) served as reference. Higher levels of tau were found in TBI patients vs patients with NPH. A correlation was found between initial vCSF total tau and GOSE levels (R = 0.42, p < 0.001) but not between vCSF total tau and NIHSS or Bartel scores at 1 year. A vCSF total tau level of >2,126 pg/mL on days 2 to 3 discriminated between dead and alive (sensitivity of 100% and a specificity of 81%). A vCSF total tau level of >702 pg/mL on days 2 to 3 discriminated between bad (GOSE 1 to 4) and good (GOSE 5 to 8) outcome (sensitivity of 83% and a specificity of 69%). Patients with GOSE 1 (dead) had higher vCSF total tau levels on days 2 to 3 (p < 0.001) vs both surviving patients (GOSE 2 to 8) and those with NPH. Total tau was not detected in serum throughout the study. The increase in ventricular CSF (vCSF) total tau probably reflects axonal damage, known to be a central pathologic mechanism in traumatic brain injury (TBI). These results suggest that vCSF total tau may be an important early biochemical neuromarker for predicting long-term outcome in patients with a severe TBI.