Cerebrospinal Fluid Tau Protein Concentrations Research Articles

Elevated Cerebrospinal Fluid Tau Protein Concentrations on Admission Are Associated With Long-term Neurologic and Cognitive Impairment in Ugandan Children With Cerebral Malaria.

Elevated concentrations of cerebrospinal fluid (CSF) tau, a marker of axonal injury, have been associated with coma in severe malaria (cerebral malaria [CM]). However, it is unknown whether axonal injury is related to long-term neurologic deficits and cognitive impairment in children with CM. Admission CSF tau concentrations were measured in 145 Ugandan children with CM and compared to clinical and laboratory factors and acute and chronic neurologic and cognitive outcomes. Elevated CSF tau concentrations were associated with younger age, increased disease severity (lower glucose and hemoglobin concentrations, malaria retinopathy, acute kidney injury, and prolonged coma duration, all P < .05), and an increased CSF:plasma albumin ratio, a marker of blood-brain barrier breakdown (P < .001). Admission CSF tau concentrations were associated with the presence of neurologic deficits at hospital discharge, and at 6, 12, and 24 months postdischarge (all P ≤ .02). After adjustment for potential confounding factors, elevated log10-transformed CSF tau concentrations correlated with worse cognitive outcome z scores over 2-year follow-up for associative memory (β coefficient, -0.31 [95% confidence interval [CI], -.53 to -.10]) in children <5 years of age, and for overall cognition (-0.69 [95% CI, -1.19 to -.21]), attention (-0.78 [95% CI, -1.34 to -.23]), and working memory (-1.0 [95% CI, -1.68 to -.31]) in children ≥5 years of age (all P < .006). Acute axonal injury in children with CM is associated with long-term neurologic deficits and cognitive impairment. CSF tau concentrations at the time of the CM episode may identify children at high risk of long-term neurocognitive impairment.

Assessment of 18F-Florbetaben Amyloid PET Imaging in Patients with Suspected Alzheimer’s Disease and Isolated Increase in Cerebrospinal Fluid Tau Proteins

The aim of this study was to assess, in routine, the rates with which an amyloid deposition was documented by 18F-florbetaben PET in patients with suspected Alzheimer's disease (AD) but with isolated increases in cerebrospinal fluid (CSF) tau-protein concentrations, and the subsequent impact of these PET results on medical management. This prospective study included 34 patients with mild neurocognitive disorders (MND) and suspected AD (73±9 years, 16 women) and with abnormal CSF concentrations in total-tau (T-tau) and/or phosphorylated-tau (P-tau) proteins but normal Aβ42 concentration and Aβ42/Aβ40 ratio. These patients were referred to 8F-florbetaben PET from which the PET-related changes in the confidence for AD diagnosis (low, intermediate, or high) and treatments were reported. The PET examinations were positive for amyloid deposition (brain amyloid plaque load, BAPL score >1) in none of the 9 patients with an increase in only T-tau proteins and in 8 among the 25 (32%) with an increase in P-tau proteins (one BAPL score of 2 and seven BAPL scores of 3). Knowledge of the PET results was associated with subsequent changes in diagnostic confidence in 44% of patients (15/34) and in the intention-to-treat with a cholinesterase inhibitor drug in 18% (6/34). In patients with suspected AD and isolated increase in CSF tau protein concentrations, an amyloid deposition is documented by 18F-florbetaben PET in as much as one third of cases when the concentration of P-tau is abnormal, and PET results are associated with significant further changes in medical management.

Tau protein (MAPT) as a possible biochemical marker of traumatic brain injury in postmortem examination

MAPT is a neuronal protein that plays an important role in axonal stabilization, neuronal development, and neuronal polarity. MAPT release into the CSF and blood has been interpreted as indicative of axonal injury as its elevated levels were observed in olympic boxers even after a mild head trauma suggesting minor CNS injuries. In our study we wanted to check the potential relevance of MAPT examination for forensic purposes. The study was carried out using cases of head injury group and cases of sudden death (cardiopulmonary failure, no injuries of the head — control group) provided by forensic pathologists at the Department of Forensic Medicine, Medical University of Warsaw. CSF and blood were collected within 24h after death using suboccipital puncture and femoral vein puncture. Serum and cerebrospinal fluid Tau protein concentrations were compared using an enzyme-linked immunosorbent assay (elisa). Brain specimens (frontal cortex) were collected during forensic autopsies. Sections were stained histologically (hematoxylin-eosin) and immunohistochemically with anti human Tau antibody, anti glial fibrillary acid protein (GFAP), anti human macrosialin (CD68) or anti human endothelial cells (CD34). In our study we documented that elevated levels of serum and CSF MAPT may also be considered a marker for mild traumatic brain injury and traumatic brain injury (mTBI and TBI). An increase in CSF and serum levels of MAPT in the absence of visible macroscopic traumatic CNS changes indicates that even minor head injuries may result in changes at the neuronal level that could remain undiagnosed during regular forensic autopsy and routine histopathological examination.

Tau protein concentrations in the cerebrospinal fluid of children with acute disseminated encephalomyelitis

Background: Acute disseminated encephalomyelitis (ADEM) is clinically characterized by the acute onset of neurological symptoms after a viral infection or immunization, and is thought to represent an autoimmune disease directed against myelin. Tau protein is a phosphorylated microtubule-associated protein, primarily located in neuronal axons. Increased levels of tau protein in cerebrospinal fluid (CSF) are found in various pathological conditions. Methods: We used tau protein as a marker of axonal damage and examined its concentration in the CSF of 27 children with ADEM. Results: CSF tau protein concentration in children with ADEM was significantly higher than that in the CSF of control subjects (P=0.008). There were no significant differences in CSF tau protein concentrations in the ADEM patients with and without encephalopathy. The CSF tau protein concentration in patients with partial lesion resolution in follow-up brain MRI was significantly higher than in patients with complete lesion resolution (P=0.014). Conclusions: In conclusion, we demonstrated that CSF tau protein concentration was significantly increased in ADEM patients. Our findings suggest that axonal damage may occur in addition to demyelination in children with ADEM.

Tau protein in cerebrospinal fluid from semantic dementia patients

Apolipoprotein E (APOE) genotypes and cerebrospinal fluid (CSF) tau protein concentration were evaluated in patients suffering from semantic dementia, with the aim of determining whether these markers could help to differentiate this condition from Alzheimer's disease (AD) in early stages. By strictly following diagnostic criteria for semantic dementia, we found a clinically homogeneous group comprising eight patients from a total population of 621 subjects referred for dementia investigation. CSF tau protein concentrations were moderately increased with a small intraindividual variation 437±36 pg/ml (mean±SD) compared to healthy control individuals. APOE genotype distribution showed an over representation of the ε4 allele (69% ε3, 31% ε4 and no ε2), a pattern similar to that found in AD. These results indicate that semantic dementia is a rather uncommon but clinically distinct condition which shows a moderate increase of CSF tau protein levels and for which the ε4 allele is a risk factor.

Relationship between apoE genotype and CSF β-amyloid (1–42) and tau in patients with probable and definite Alzheimer’s disease

We investigated the usefulness of cerebrospinal fluid (CSF) β-amyloid42 (Aβ42), β-amyloid40 (Aβ40) and tau analyses in the diagnosis of Alzheimer’s disease (AD). The study included 41 definite AD cases, 80 patients with probable AD, 27 with other dementias and 39 neurological controls. Aβ42, Aβ40 and tau protein concentrations in CSF were measured of using ELISA assays. Aβ42 levels were decreased and tau increased in AD. Combination of Aβ42 and tau resulted a sensitivity of 50.4% for AD and specificities of 94.8% for controls and 85.2% for other dementias. Ninety-one percent of the patients with Aβ42 below the cutoff value (340 pg/ml) and tau above the cutoff value (380 pg/ml) had AD. AD patients carrying apoE ϵ4 allele had lower Aβ42 ( P < 0.005) and higher tau ( P < 0.05) levels than those without an ϵ4 allele, and 18 (81.8%) of the 22 AD patients who had normal Aβ42 and tau levels were apoE ϵ4 allele non-carriers. Low Aβ42 and high tau concentration in CSF strongly support the diagnosis of AD. Measurement of Aβ42 may help the early diagnosis of cases at risk for AD such as apoE ϵ4 allele carriers.

Three-year follow-up of cerebrospinal fluid tau, β-amyloid 42 and 40 concentrations in Alzheimer's disease

Earlier studies have shown elevated levels of tau protein and decreased levels of amyloid β42 in cerebrospinal fluid (CSF) from patients with Alzheimer's disease (AD). We investigated the concentrations of A β42, A β40 and tau in CSF from AD patients on the baseline and after follow-up period of 3 years using ELISA assays. There was a significant decrease of A β42 ( P<0.05) and A β40 ( P<0.05) levels with time. AD patients with the duration of the disease 2 years or less at baseline had more pronounced decrease of A β42 concentrations compared to those with the duration of the disease more than 2 years at baseline ( P<0.05). CSF tau protein concentrations increased in 9/17 but decreased in 8/17 patients. These results suggest that A β42 and A β40 may be useful in monitoring the long-term progression of AD particularly in the early stages of the disease.

Tau protein concentrations in cerebrospinal fluid of non-demented Parkinson's disease patients

We measured total tau protein concentrations in the cerebrospinal fluid (CSF) of 26 non-demented Parkinson's disease (PD) patients and 25 matched controls. When compared with controls, PD patients had similar CSF tau protein concentrations. These values were not correlated with age, age at onset of PD, duration of PD, scores of the Unified PD Rating Scale (UPDRS), and the Hoehn and Yahr staging, and were not influenced significantly by antiparkinsonian drugs. Our results suggest that CSF tau protein levels are apparently unrelated to the risk of PD.

Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease

Creutzfeldt–Jakob disease (CJD) is a rare, fatal, neurodegenerative disease caused by a transmissible agent designated as proteinaceous infectious agent (prion). Searching for biochemical markers of CJD, we analysed cerebrospinal fluid (CSF) samples of 53 patients for tau-protein using an enzyme linked immunoassay (ELISA). In a group of 21 patients with definite CJD seen in the German case control study for CJD, tau-protein concentrations in CSF were significantly higher than in two control-groups of patients with other diseases (median 13153 pg/ml, range 1533–27648 pg/ml; P=0.0001). One control group comprised 19 patients who were seen in the same study and were diagnosed as having other dementing diseases (tau concentration: median 558 pg/ml, range 233–1769 pg/ml). The second control group comprised 13 patients from our hospital with no dementing disease (tau concentration: median 296 pg/ml, range 109–640 pg/ml). We conclude that determination of tau protein levels in CSF is a useful marker for laboratory diagnosis of CJD.