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Abstract: Purpose: Whether repeated brief seizures can cause neuronal damage is controversial. Cerebrospinal fluid (CSF) total tau (T-tau) and phosphorylated tau (P-tau) measurements have been suggested for the diagnosis of Alzheimer''s disease, and T-tau may also be a marker of axonal damage and neuronal degeneration. We studied T-tau and P-tau levels and P-tau/T-tau ratio in CSF after epileptic seizures in order to determine whether they are increased after seizures. Methods: A total of 54 patients with tonic–clonic or partial secondarily generalized seizures due to various etiologies were studied and CSF obtained within 48h after the seizure. Results: There were no statistical differences in the levels of T-tau (p =0.09, ANOVA) or P-tau (p =0.60) between different etiologic groups or controls. No patients with epilepsy of unknown origin had abnormal CSF T-tau whereas 11 patients with acute or remote symptomatic seizures had abnormal T-tau levels and the P-tau/T-tau ratio showed significant differences between the groups and controls (p =0.003). Conclusions: Epileptic seizures with unknown etiology did not increase CSF tau levels. Abnormal tau levels were associated with either acute or remote symptomatic seizures with known etiology. The presence of elevated CSF tau increases the probability of symptomatic cause in a patient with a seizure. [Copyright &y& Elsevier]

A protocol for quantitative 1H NMR analysis of human cerebrospinal fluid (hCSF) was built up and assessed as based on Constrained Total-Line-Shape (CTLS) fitting. In this method, linear constraints were applied to spectral structures. The 1H NMR spectra of 45 human CSF samples were measured and quantified using the CTLS method. The quantification strategies based on total-line-shape fitting are discussed. The metabolic model for CTLS includes 31 metabolites covering 85% of the total spectral intensity, excluding the protein contribution. Prior to data analysis, the data was divided into patients with no Alzheimer’s disease (AD), but with a normal AD marker profile (the peptide β-amyloid42 and tau protein) present in CSF, and into controls that do not have an AD marker profile in CSF. Unexpectedly large variations in metabolite concentrations within the two patient groups were detected, but an analysis of variance revealed a significant ( P = 0.027) difference only in the concentration of creatinine which was higher in patients that had a normal AD marker profile. Multivariate classification tools such as self-organizing maps (SOM) failed in separation of the two classes. [ABSTRACT FROM AUTHOR]

Cerebrospinal fluid (CSF) biomarkers and medial temporal lobe (MTL) atrophy predict the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD). We investigated the association between the CSF biomarkers and MTL atrophy and the ability of these measures to predict AD in MCI patients in the same study population. The study included 21 MCI patients of whom eight progressed to AD during the study. CSF biomarkers were measured by using ELISA method and volumes of MTL structures were assessed by magnetic resonance imaging (MRI). Aβ42 levels were lower and tau and phospho-tau levels were higher in progressive subjects. The progressive subjects had lower volumes in all MRI measures. Tau and phospho-tau correlated inversely with hippocampal volumes and left entorhinal cortex volume in the whole study group. In the stable group, tau correlated with hippocampal volumes. Aβ42 had a negative correlation whereas phospho-tau exhibited a positive correlation with left hippocampal volume in the progressive group. These results indicate that both measures may reflect the ongoing neurodegenerative process in the progressive MCI patients. However, the order of the changes in the CSF biomarkers and MTL atrophy remain unclear due to a small number of studied subjects and study design. [ABSTRACT FROM AUTHOR]

Background: Phosphorylation of tau protein at threonine 231 (using full-length tau, 441 amino acids, for the numbering scheme) (p-tau[sub 231]) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF). Objectives: To determine to what extent CSF levels of p-tau[sub 231] distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-tau[sub 231] levels are a better diagnostic marker than levels of total tau protein (t-tau) in CSF. Design and Setting: Cross-sectional, multicenter, memory clinic–based studies. Participants: One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls. Main Outcome Measures: Levels of CSF tau proteins as measured with enzyme-linked immunosorbent assays. Results: Mean CSF levels of p-tau[sub 231] were significantly elevated in the AD group compared with all other groups. Levels of p-tau[sub 231] did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-tau[sub 231] levels improved diagnostic accuracy compared with t-tau levels when patients with AD were compared with healthy controls (P = .03) and demented subjects (P<.001), particularly those with FTD (P<.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-tau[sub 231] compared with t-tau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers. Conclusion: Increased levels of CSF p-tau[sub 231] may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD. [ABSTRACT FROM AUTHOR]

Background: In brains with AD, Aβ is a major component of diffuse plaques. Previous reports showed that CSF Aβ42 levels were lower in patients with AD than in controls. Although studies showed higher plasma Aβ42 levels in familial AD, a recent report has indicated that plasma Aβ42 levels were similar in a sporadic AD group and controls. However, no information is published on plasma Aβ40 and Aβ42 levels in relation to Apo E genotype or severity of dementia in sporadic AD. Objective: To examine plasma and cerebrospinal fluid (CSF) levels of amyloid β protein 1-40 (Aβ40) and 1-42 (Aβ42) levels in patients with probable Alzheimer disease (AD) and elderly nondemented control subjects in relation to the apolipoprotein E (Apo E) genotype and dementia severity. Setting: Two university medical centers. Patients and Methods: Levels of Aβ40 and Aβ42 were measured in plasma from 78 patients with AD and 61 controls and in CSF from 36 patients with AD and 29 controls by means of a sandwich enzyme-linked immunosorbent assay. Results: Mean plasma Aβ40 levels were higher in the AD group than in controls (P = .005), but there was substantial overlap; Aβ42 levels were similar between the groups. Levels of Aβ40 and Aβ42 showed no association with sex or Mini-Mental State Examination scores. There was a significant relationship between age and Aβ40 level in controls but not in the AD group. Levels of Aβ40 were higher in patients with AD with the Apo E ε4 allele than in controls (P<.01). Cerebrospinal fluid Aβ40 levels were similar in the AD group and controls. However, Aβ42 levels were lower in the AD group than in controls (P<.001). The levels showed no association with severity of dementia. Conclusions: Although mean plasma Aβ40 levels are elevated in sporadic AD and influenced by Apo E genotype, measurement of plasma Aβ40 levels is not useful ... [ABSTRACT FROM AUTHOR]

Abstract: Recently, the P86L alteration in CALHM1 (calcium homeostasis modulator-1) was reported to be associated with Alzheimer''s disease (AD). Moreover, the risk allele increased amyloid-β (Aβ) levels in conditioned media from cultured cells. Therefore, we hypothesized that CALHM1 P86L may modulate Aβ or tau levels in cerebrospinal fluid (CSF). Nearly 200 individuals with AD or other cognitive disorders were included for CSF analysis and CALHM1 genotyping. No significant differences in CSF levels of Aβ42, tau or phospho-tau were found across the various CALHM1 genotypes. In conclusion, we found no evidence that CALHM1 P86L is associated with altered CSF levels of the investigated AD biomarkers. [Copyright &y& Elsevier]