Cerebrospinal Fluid Tau Protein Levels Research Articles

Late-onset temporal lobe epilepsy: insights from brain atrophy and Alzheimer's disease biomarkers.

Considering the growing age of the world population, the incidence of epilepsy in older adults is expected to increase significantly. It has been suggested that late-onset temporal lobe epilepsy (LO-TLE) may be neurodegenerative in origin and overlap with Alzheimer's Disease (AD). Herein, we aimed to characterize the pattern of cortical atrophy and cerebrospinal fluid (CSF) biomarkers of AD (total and phosphorylated tau, and β-amyloid) in a selected population of LO-TLE of unknown origin. We prospectively enrolled individuals with temporal lobe epilepsy onset after the age of 50 and no cognitive impairment. They underwent a structural MRI scan and CSF biomarkers measurement. Imaging and biomarkers data were compared to three retrospectively collected groups: (i) age-sex-matched healthy controls, (ii) patients with Mild Cognitive Impairment (MCI) and abnormal CSF AD biomarkers (MCI-AD), and (iii) patients with MCI and normal CSF AD biomarkers (MCI-noAD). From a pool of 52 patients, twenty consecutive eligible LO-TLE patients with a mean disease duration of 1.8 years were recruited. As control populations, 25 patients with MCI-AD, 25 patients with MCI-noAD, and 25 healthy controls were enrolled. CSF biomarkers returned normal values in LO-TLE, significantly different from patients with MCI due to AD. There were no differences in cortico-subcortical atrophy between epilepsy patients and healthy controls, while patients with MCI demonstrated widespread injuries of cortico-subcortical structures. Individuals with a late-onset form of temporal lobe epilepsy, characterized by short disease duration and normal CSF β-amyloid and tau protein levels, showed patterns of cortical thickness and subcortical volumes not significantly different from healthy controls, but highly different from patients with MCI, either due to Alzheimer's Disease or not.

High-dimensional generalized median adaptive lasso with application to omics data.

Recently, there has been a growing interest in variable selection for causal inference within the context of high-dimensional data. However, when the outcome exhibits a skewed distribution, ensuring the accuracy of variable selection and causal effect estimation might be challenging. Here, we introduce the generalized median adaptive lasso (GMAL) for covariate selection to achieve an accurate estimation of causal effect even when the outcome follows skewed distributions. A distinctive feature of our proposed method is that we utilize a linear median regression model for constructing penalty weights, thereby maintaining the accuracy of variable selection and causal effect estimation even when the outcome presents extremely skewed distributions. Simulation results showed that our proposed method performs comparably to existing methods in variable selection when the outcome follows a symmetric distribution. Besides, the proposed method exhibited obvious superiority over the existing methods when the outcome follows a skewed distribution. Meanwhile, our proposed method consistently outperformed the existing methods in causal estimation, as indicated by smaller root-mean-square error. We also utilized the GMAL method on a deoxyribonucleic acid methylation dataset from the Alzheimer's disease (AD) neuroimaging initiative database to investigate the association between cerebrospinal fluid tau protein levels and the severity of AD.

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.

Cerebrospinal Fluid Total Tau Protein Correlates With Longitudinal, Progressing Cognitive Dysfunction in Anti-Neural Autoantibody-Associated Dementia and Alzheimer's Dementia: A Case-Control Study.

BackgroundNeural autoantibody-associated dementia (NABD) is an increasing phenomenon in memory clinics with a high impact on later therapy. Biomarkers are lacking that differentiate this type of dementia from neurodegenerative dementia such as Alzheimer’s dementia (AD). Our aim is to analyze neurodegeneration markers and their relationship to progressing cognitive dysfunction in NABD and AD to test for tools differentiating these two forms of dementia prior to neural autoantibody testing.MethodsIn our retrospective, observational study, we investigated 14 patients with dementia and serum and/or cerebrospinal fluid (CSF) neural autoantibodies as well as 14 patients with AD by relying on recent CSF and clinical criteria for AD. Patient files were checked for psychopathology, neuropsychological test performance, autoimmune indicators, CSF, and MRI results.ResultsOur patient groups did not differ in their psychopathology, autoimmune indicators, or MRI profile. The progression of cognitive dysfunction [as measured by the difference in Mini-Mental State Examination (MMSE) scores since disease onset, and the yearly progression rate (MMSE loss/per year)] did not vary significantly between groups. Total tau protein was significantly higher in AD patients than NABD patients revealing no signs of Alzheimer’s disease pathology in their CSF (p < 0.05). Total tau protein levels in CSF correlated with cognitive decline since disease onset (r = 0.38, p < 0.05) and yearly progression rates (r = 0.56, p < 0.005) in all patients.DiscussionOur results suggest that the progression of cognitive dysfunction as defined by MMSE does not seem to be an appropriate biomarker for distinguishing NABD from AD. However, the total tau protein level in CSF might be a relevant molecular biomarker that can indicate disease pathology and/or progression in both known AD and NABD, which is often accompanied by axonal degeneration. Total tau protein may be an additional diagnostic tool with which to differentiate anti-neural-associated dementia from AD if further research confirms these proof-of-concept findings in larger patient cohorts.

Role of cerebrospinal fluid tau protein levels as a biomarker of brain injury in pediatric status epilepticus

Background Various biomarkers have been studied for predicting etiology and outcome in status epilepticus (SE); cerebrospinal fluid (CSF) total tau (t-tau) protein levels is foremost among them. Only handful of studies are available regarding role of t-tau in childhood SE. Methodology This prospective study was conducted in a tertiary care center of Northern India in children 6 months −12 years of age. The Cases were patients with convulsive status epilepticus (CSE) whereas Controls were patients without SE and normal CSF. The t-tau levels were done in CSF of both the groups. The outcome was assessed by GOS-E Peds score. Results A total of 50 (62% males) cases and 15 (67% males) controls were enrolled in the study. SE was generalized in 78% cases whereas 14% had refractory SE. Most common etiology of CSE was acute symptomatic (52%), followed by prolonged febrile seizure (24%), remote symptomatic group (14%), unknown etiology (8%) and progressive disorder (2%). Case fatality rate was 10%. Poor outcome was seen in 30% cases. Median (IQR) CSF t-tau levels was significantly lower 2.6 × 103 (0.5–9.4 × 103) pg/ml in cases vs 10.6 × 103 (6.0–14.2 × 103) pg/ml in controls (p = 0.004). There was no significant correlation seen between type, duration, etiology and response to antiepileptic drugs of SE with CSF t-tau levels. Also, no significant correlation of poor sensorium, outcome of SE and critical care needs with CSF t-tau levels was noted. Conclusion CSF t-tau is not a useful diagnostic or prognostic biomarker in pediatric SE.

Retinopathy-Positive Cerebral Malaria Is Associated With Greater Inflammation, Blood-Brain Barrier Breakdown, and Neuronal Damage Than Retinopathy-Negative Cerebral Malaria.

Our prior study findings suggest that Plasmodium falciparum is the cause of disease in both malaria retinopathy-positive (RP) and most retinopathy-negative (RN) cerebral malaria (CM), and that absence of retinopathy and decreased disease severity in RN CM may be due to shorter duration of illness, lower parasite biomass, and decreased var gene expression in RN compared to RP CM. In the present study, we assessed the pathophysiology of RP and RN CM. We compared markers of systemic and central nervous system inflammation, oxidative stress, neuronal injury, systemic endothelial activation, angiogenesis, and platelet activation in Ugandan children with RP (n = 167) or RN (n = 87) CM. RP children had higher plasma C-reactive protein (P = .013), ferritin and erythropoietin (both P < .001) levels, an elevated cerebrospinal fluid (CSF):plasma albumin ratio (P < .001), and higher CSF tau protein levels (P = .049) than RN children. Levels of plasma and CSF proinflammatory and anti-inflammatory cytokines and oxidative stress markers did not differ between RP and RN children. RN children had higher plasma levels of endothelin 1 (P = .003), platelet-derived growth factor (P = .012), and platelet factor 4 (P = .034). RP and RN CM may represent different phases of CM. RN CM may be driven by early vasospasm and platelet activation, whereas the more advanced RP CM is associated with greater inflammation, increased erythropoietic drive, blood-brain barrier breakdown, and neuronal injury, each of which may contribute to greater disease severity.

Unusual presentations in patients with E200K familial Creutzfeldt-Jakob disease.

Familial Creutzfeldt-Jakob disease (fCJD) in Jews of Libyan ancestry is caused by an E200K mutation in the PRNP gene. The typical presenting symptoms include cognitive decline, behavioral changes and gait disturbances; however, some patients may have an unusual presentation such as a stroke-like presentation, alien hand syndrome or visual disturbances. The aim of this paper is to describe uncommon presentations in our series of consecutive patients with E200K fCJD. The study group included consecutive fCJD patients followed up as part of a longitudinal prospective study ongoing since 2003 or hospitalized since 2005. The clinical diagnosis of probable CJD was based on accepted diagnostic criteria and supported by typical magnetic resonance imaging, electroencephalographic findings, elevated cerebrospinal fluid tau protein levels and by genetic testing for the E200K mutation. Disease symptoms and signs were retrieved from the medical files. The study population included 77 patients (42 men) with a mean age of disease onset of 60.6 ± 7.2 years. The most prevalent presenting symptoms were cognitive decline followed by gait impairment and behavioral changes. However, six patients had an unusual presentation including auditory agnosia, monoparesis, stroke-like presentation, facial nerve palsy, pseudobulbar syndrome and alien hand syndrome. Our case series illustrates the wide phenotypic variability of the clinical presentation of patients with fCJD and widens the clinical spectrum of the disease. A high level of clinical suspicion may prove useful in obtaining early diagnosis and therefore avoiding costly and inefficient diagnostic and therapeutic strategies.

Amyloid-β Peptides and Tau Protein as Biomarkers in Cerebrospinal and Interstitial Fluid Following Traumatic Brain Injury: A Review of Experimental and Clinical Studies

Traumatic brain injury (TBI) survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in many severe TBI patients, results in accumulation of amyloid precursor protein (APP). Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ) peptides, a hallmark finding in Alzheimer’s disease (AD). At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF) using cerebral microdialysis and/or cerebrospinal fluid (CSF) following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques, and the complexity of TBI in the available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using methods such as rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long-term consequences of TBI.

Intellectual functioning of childhood leukemia survivors - relation to Tau protein - a marker of white matter injury

Chemo- and radiotherapy used in acute lymphoblastic leukemia (ALL) can influence on brain functioning in the future. In a prospective study we analysed the cognitive functions of ALL survivors in relation to Tau protein as a marker of white matter injury. Thirty-one survivors of childhood ALL (6.3 years after diagnosis); without the signs of CNS involvement, treated with chemotherapy alone, rested in first remission; underwent Intelligence tests- Wechsler Intelligence Scales (WISC-R, WAIS-R). Their results were analyzed in relation to the levels of Tau in cerebrospinal fluid (CSF) obtained during the treatment. The analysis showed that all survivors attained the average scores in intelligence tests. A negative correlation was found between methotrexate (MTX) doses and Freedom from Distractibility (FFD). Females had higher values of Performance Intelligence Quotient (PIQ) than males. A negative correlation was noted of Tau protein levels obtained from the last CSF with: Total and Verbal Intelligence Quotient, PIQ, Perceptual Organisation Index and FFD but not with Verbal Comprehension Index. Our results suggest the possibility of white matter injury during the treatment for ALL with chemotherapy alone. Elevated Tau protein level in CSF at the end of treatment might indicate future difficulties in neurocognitive functioning.

Cerebrospinal Fluid Proteins Predict Longitudinal Hippocampal Degeneration in Early-stage Dementia of the Alzheimer Type

Biomarkers are needed to improve the sensitivity and accuracy of diagnosis, and also prognosis, in individuals with early Alzheimer disease (AD). Measures of brain structure and disease-related proteins in the cerebrospinal fluid (CSF) have been proposed as biomarkers, yet relatively little is known about the relationships between such measures. The present study was conducted to assess the relationship between CSF Aβ and tau protein levels and longitudinal measures of hippocampal structure in individuals with and without very mild dementia of the Alzheimer type. A single CSF sample and longitudinal magnetic resonance scans were collected. The CSF samples were assayed for tau, phosphorylated tau181 (p-tau181), Aβ1-42, and Aβ1-40 using an enzyme-linked immunosorbent assay. Large-deformation diffeomorphic metric mapping was used to generate hippocampal surfaces, and a composite hippocampal surface (previously constructed from 86 healthy participants) was used as a structural reference. Thirteen participants with very mild AD (Clinical Dementia Rating, CDR 0.5) and 11 cognitively normal participants (CDR 0). None. Initial and rate-of-change measures of total hippocampal volume and displacement of the hippocampal surface within zones overlying the CA1, subiculum, and CA2-4+DG cellular subfields, and their correlations with initial CSF measures. Lower CSF Αβ1-42 levels and higher tau/Αβ1-42 and p-tau181/Αβ1-42 ratios were strongly correlated with decreases in hippocampal volume and measures of progressive inward deformations of the CA1 subfield in participants with early AD, but not in cognitively normal participants. Despite the small sample size, we found that Αβ1-42 related and tau-related CSF measures were associated with hippocampal degeneration in individuals with clinically diagnosed early AD and may reflect an association with a common underlying disease mechanism.

Elevated Cerebrospinal Fluid Tau Protein Levels in Wernicke’s Encephalopathy

Limited neuronal cell loss is seen in the neuropathology of Wernicke's encephalopathy (WE), but the extent of neuronal damage has not been well studied. Moreover, there is still a debate as to whether alcohol itself causes brain damage in humans. Although, it is difficult to examine the extent of neuronal damage in living patients, recent studies have revealed that total tau protein levels in the cerebrospinal fluid (CSF) reflect the rate of neuronal degeneration. Therefore, we hypothesized that the elevated CSF total tau in patients with WE was due to neuronal damage and thus we examined CSF total tau protein in patients with WE, as well as in those with alcohol withdrawal delirium (WD) and Korsakoff syndrome (KS). We also examined CSF total tau in nonalcohol dependent patients with Alzheimer's disease (AD) as a disease control. CSF samples were obtained from 13 acute WE patients with alcohol dependence, 9 WD patients with alcohol dependence and 16 KS patients with alcohol dependence, and from 20 nonalcohol dependent AD patients. CSF was also obtained from 10 of the WE patients after their disease had progressed to the chronic stage. CSF tau protein levels in all samples were determined by sandwich enzyme-linked immunosorbent assay. Tau phosphorylated at threonine 181 (p-tau(181)) and amyloid beta-protein ending at amino acid 42 (A beta 42) in CSF were also determined for comparison between acute WE with AD. Total tau was significantly elevated in acute WE and decreased on long-term follow-up, but was not elevated in WD or KS. The patterns of p-tau(181) and A beta 42 differed between acute WE and AD. Intense neuronal cell death occurs transiently in WE, and the mechanism differs from that in AD. Neuronal damage is generally unaccompanied in WD. These results suggest that CSF total tau is a useful biological marker for WE.

Serum Heart-Type Fatty Acid-Binding Protein and Cerebrospinal Fluid Tau: Marker Candidates for Dementia with Lewy Bodies

Background: The measurement of biomarkers in cerebrospinal fluid (CSF) has gained increasing acceptance in establishing the diagnosis of some neurodegenerative diseases. Heart-type fatty acid-binding protein (H-FABP) was recently discovered in CSF and serum of patients with neurodegenerative diseases. Objective: We investigated H-FABP in CSF and serum alone and in combination with CSF tau protein to evaluate these as potential biomarkers for the differentiation between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). Methods: We established H-FABP and tau protein values in a set of 144 persons with DLB (n = 33), Parkinson disease with dementia (PDD; n = 25), AD (n = 35) and nondemented neurological controls (NNC; n = 51). Additionally, serum H-FABP levels were analyzed in idiopathic Parkinson disease patients without evidence of cognitive decline (n = 45) using commercially available enzyme-linked immunosorbent assays. We calculated absolute values of H-FABP and tau protein in CSF and serum and established relative ratios between the two to obtain the best possible match for the clinical working diagnosis. Results: Serum H-FABP levels were elevated in DLB and PDD patients compared with NNC and AD subjects. To better discriminate between DLB and AD, we calculated the ratio of serum H-FABP to CSF tau protein levels. At the arbitrary chosen cutoff ratio ≧8 this quotient reached a sensitivity of 91% and a specificity of 66%. Conclusion: Our results suggest that the measurement of CSF tau protein, together with H-FABP quantification in serum and CSF, and the ratio of serum H-FABP to CSF tau protein represent marker candidates for the differentiation between AD and DLB.

Tau Protein, Aβ42 and S-100B Protein in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies

The intra vitam diagnosis of dementia with Lewy bodies (DLB) is still based on clinical grounds. So far no technical investigations have been available to support this diagnosis. As for tau protein and β-amyloid_(1–42) (Aβ42), promising results for the diagnosis of Alzheimer’s disease (AD) have been reported; we evaluated these markers and S-100B protein in cerebrospinal fluid (CSF), using a set of commercially available assays, of 71 patients with DLB, 67 patients with AD and 41 nondemented controls (NDC) for their differential diagnostic relevance. Patients with DLB showed significantly lower tau protein values compared to AD but with a high overlap of values. More prominent differences were observed in the comparison of DLB patients with all three clinical core features and AD patients. Aβ42 levels were decreased in the DLB and AD groups versus NDC, without significant subgroup differences. S-100B levels were not significantly different between the groups. Tau protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited especially due to mixed pathology. We conclude that more specific markers have to be established for the differentiation of these diseases.

Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias.

Early clinical symptoms of sporadic Creutzfeldt-Jakob disease (CJD) may overlap with other neurodegenerative diseases like Alzheimer's disease (AD) and frontotemporal degeneration (FTD). On entering an era in which pharmaceutical treatment of CJD occurs, reliable diagnostic markers like immunodetection of 14-3-3 proteins in the cerebrospinal fluid (CSF) are required. However, false negative results in autopsy-proven, sporadic CJD cases, as well as false positive results in several other disorders including AD and FTD showing high CSF tau protein levels, limit the potential of this marker. Due to neuronal lysis the cytosolic fraction of total tau containing phosphorylated and non-phosphorylated isoforms is partially liberated into the CSF. Since hyperphosphorylation of tau may specifically occur in neurodegenerative diseases associated with neurofibrillary changes, we hypothesized that the phospho-tau (P-tau)/total tau ratio in CSF may be a useful marker to discriminate CJD from other neurodegenerative disorders. The P-tau/total tau ratio discriminated patients with CJD from all other neuro-degenerative disorders including patients with AD and FTD without any overlap. Although the results have to be confirmed in a larger sample, the preliminary data suggest that simultaneous measurement of total tau and P-tau in CSF may be useful to identify patients with CJD.

Levels of total tau and tau protein phosphorylated at threonine 181 in patients with incipient and manifest Alzheimer's disease

Cerebrospinal fluid tau protein levels are considered to be a promising marker for Alzheimer's disease (AD) and may facilitate early detection. Using the newly developed INNOTEST Phospho-Tau (181P) kit examination of total tau and tau protein phosphorylated at threonine 181 (phospho-tau 181) revealed significantly ( P<0.05) higher values in both patients with incipient and manifest AD than in controls. In patients with vascular dementia, phospho-tau 181 levels were not different from controls but were significantly lower than in patients with manifest AD. These findings suggest that total and phosphorylated tau protein may facilitate early detection and differential diagnosis of AD.

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.

Detection of oligomeric β-amyloid peptide in biological samples using a singlesite monoclonal antibody sandwich enzyme-linked immunoabsorbant assay

Apolipoprotein E (apoE) levels were compared in cerebrospinal fluid (CSF) taken on two occasions, with an average 15 months follow up, from groups of patients with Alzheimer's disease (AD; n=18), mild cognitive impairment (MCI; n=9) and other dementia disorders (ODD; n=9). In these groups, CSF apoE levels were between 2–3-fold higher than values for a group of 27 healthy age-matched controls. CSF apoE levels in the AD group were significantly increased at follow up, compared to levels obtained on the first sampling occasion. For the same cases it had been shown previously that CSF tau protein levels were increased at follow up [Blomberg, M., Jensen, M., Basun, H., Lannfelt, L. and Wahlund, L-O., Neurosci. Lett., 214 (1996) 163–166]. The AD, but not MCI, ODD or control groups, also showed statistically significant correlations between CSF apoE and tau protein levels at both the first (r=0.585, P<0.01) and follow up (r=0.695, P>0.001) samplings. It is concluded that CSF measures of both apoE and tau may reflect an intimate relationship between these two proteins in AD and could prove useful in monitoring the progression of this condition.

Increased cerebrospinal fluid cAMP levels in Alzheimer's disease

Since increasing evidence suggests that upregulation of the cAMP-second messenger system may be implicated in Alzheimer's disease neurodegeneration, we have compared the cAMP and cGMP levels in cerebrospinal fluid (CSF) from patients with dementia of the Alzheimer type (DAT, n=10) with those from nondemented age-matched controls ( n=10). Our results show that cAMP levels, but not cGMP, are significantly ( p<0.01) elevated in CSF from patients with DAT compared to those from nondemented controls. Moreover, a linear regression analysis demonstrated a significant correlation ( r=0.62; p<0.01) between cAMP and tau protein levels in CSF when controls and patients with DAT were studied together. These results suggest that upregulation of cAMP-signaling pathway is implicated in Alzheimer's disease physiopathology.

Cerebrospinal Fluid Tau Protein Levels in Demented and Nondemented Alcoholics

The tau protein levels in cerebrospinal fluid (CSF-tau) were examined in 27 patients with alcohol dependence (20 demented and 7 nondemented), 36 age and dementia severity-matched patients with Alzheimer's disease (AD), and 23 age-matched normal control subjects. The CSF-tau levels in the demented alcoholic group (alcohol-induced organic brain disorders, 25.4 +/- 10.2 pg/ml) was significantly lower (p < 0.0001) than that in the AD group (96.1 +/- 53.3 pg/ml), but not significantly different from that in the nondemented alcoholics (18.1 +/- 10.2 pg/ml) or the controls (19.2 +/- 12.9 pg/ml). Using a 44.9 pg/ml as a cut-off value (mean + 2 SD of the normal control group), only one patient with alcohol-induced organic brain disorders exceeded the value, whereas 3 of 36 of the AD group showed CSF-tau levels less than this level. These findings suggest that alcohol-induced organic brain disorders are a group of dementias that are characterized by normal CSF-tau levels, and that the CSF examination for tau in combination with other clinical findings may help in differentiating alcohol-induced organic brain disorders from AD.

No increase in cerebrospinal fluid tau protein levels in patients with vascular dementia

Tau protein levels in cerebrospinal fluid (CSF-tau) were determined in 29 patients with old cerebrovascular disease (CVD, 21 demented and eight non-demented), 69 patients with Alzheimer's disease (AD) and 17 age-matched normal controls. The CSF-tau level in the vascular dementia (VD) group (24.0±17.0 pg/ml) was significantly lower ( P<0.0001) than that in the AD group (90.0±45.3 pg/ml), but not significantly different from that in the non-demented patients with CVD (18.1±10.2 pg/ml) or controls (20.3±13.0 pg/ml). Among the VD patients, 1/21 exceeded a cut-off value (mean±2 SD of controls), whereas 8/69 of the AD patients had CSF-tau levels below this value. These findings suggest that VD constitutes a group of dementias that can be separated from AD by normal CSF-tau levels. CSF-tau determinations in combination with other clinical findings may provide another diagnostic aid in the differential diagnosis between VD and AD.