Search

To better understand the seemingly contradictory plasma β-amyloid (Aβ) results in Alzheimer’s disease (AD) patients by using a newly developed plasma Aβ assay, the INNO-BIA plasma Aβ forms, in a multicenter study. A combined retrospective analysis of plasma Aβ isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers. Detection modules based on two different amino (N)-terminal specific Aβ monoclonal antibodies demonstrated that Aβ in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low Aβ42 plasma concentrations. Aβ40 and Aβ42 concentrations varied consistently with the ApoE genotype, while the Aβ42/Aβ40 ratio did not. Irrespective of the decrease of the Aβ42/Aβ40 ratio with age and MMSE, this parameter was strongly associated with AD, as defined in this study by elevated hyperphosphorylated (P-tau181P) levels in cerebrospinal fluid (CSF). A highly robust assay for repeatedly measuring Aβ forms in plasma such as INNO-BIA plasma Aβ forms might be a useful tool in a future risk assessment of AD. [ABSTRACT FROM AUTHOR]

During the last years, several clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in Alzheimer’s disease (AD) in humans. We present an open biochemical study where 19 patients with AD have been treated with simvastatin (20 mg/day) for 12 months. The aim was to further investigate the effect of simvastatin treatment on cerebrospinal fluid (CSF) biomarkers of APP processing, AD biomarkers as total tau and tau phosphorylated at threonine 181, brain cholesterol metabolism as well as on cognitive decline in patients with AD. Despite biochemical data suggesting that treatment with 20 mg/day of simvastatin for 12 months does affect the brain cholesterol metabolism, we did not find any change in CSF or plasma levels of β-amyloid (Aβ)1–42. However, by analysis of APP isoforms, we found that statin treatment may favor the nonamyloidogenic pathway of APP processing. The relevance and mechanism between statin treatment and AD has to be further elucidated by using statins of different lipophility in different dosages over a longer period of time. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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 neurodegenerative 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. Molecular Psychiatry (2003) 8, 343–347. doi:10.1038/sj.mp.4001220. [ABSTRACT FROM AUTHOR]

Summary. Cerebrospinal fluid (CSF) levels of tau, β-amyloid1–42 and growth-associated protein 43 (GAP-43) were studied in patients with frontotemporal dementia (FTD; n = 17), Alzheimer's disease (AD; n = 60), subcortical white-matter dementia (SWD; n = 24), Parkinson's disease (PD; n = 23) and dysthymia (n = 19) and in age-matched controls (n = 32). CSF-tau was significantly increased only in AD, and CSF-β-amyloid1–42 was significantly decreased in AD and SWD as compared to controls, and in AD compared to FTD. CSF-GAP-43 was significantly decreased only in PD. The GAP-43/tau ratio was decreased in all the patient groups except the dysthymia group compared to controls. A positive correlation was found between CSF-GAP-43 and CSF-tau in all groups. The results suggest normal levels of CSF-tau and CSF-β-amyloid1–42 in FTD, which will aid in the clinical separation of FTD from AD. In SWD, decreased levels of CSF-β-amyloid1–42 suggest concomitant involvement of vascular and amyloid protein mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: Biochemical markers for Alzheimer's disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer's disease. However, the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia. As most previous CSF studies have been based on selected inpatients, it was considered of special interest to examine the diagnostic potential of CSF-tau in a community population based sample of consecutive patients with dementia. Such patient material has been examined at the Piteå River Valley Hospital in Northern Sweden since 1986, and includes all those with memory disturbances in the community. The aim was also to study if an increase in CSF-tau is found early in the disease process, and whether CSF-tau changes during the progression of disease.Methods: Participants: Community population based sample of 75 demented patients (43 with Alzheimer's disease, 21 with vascular dementia, and 11 with mixed Alzheimer's disease/vascular dementia), 18 healthy subjects, and 18 neurological controls. A follow up investigation (including analysis of a new CSF sample) was performed in all patients after about one year.Main Outcome Measures: Concentrations of total (both normal tau and PHF-tau) tau in CSF, clinical measures (duration and severity of dementia), and apoE polymorphism.Results: CSF-tau was markedly increased in Alzheimer's disease, 41/43 (95%) patients had values above the cut off level (mean+2 SD) in controls (306 pg/ml). High CSF-tau concentrations were also found in most patients with vascular dementia, preferentially in patients with vascular dementia without progressive leukoaraiosis on CT, whereas patients with vascular dementia with progressive leukoaraiosis had normal CSF-tau. Concentrations of CSF-tau were stable at one year follow up in both patients with Alzheimer's disease and patients with vascular dementia, and there was no correlation between CSF-tau and either duration or severity of dementia.Conclusions: The findings confirm the high sensitivity of CSF-tau for the diagnosis of Alzheimer's disease, but high CSF-tau was also found in vascular dementia, resulting in a lower specificity. However, high CSF-tau is preferentially found in patients with vascular dementia without progressive leukoaraiosis, which may constitute a group with concomitant Alzheimer's disease pathology. High CSF-tau may be present during the whole course of the disease in Alzheimer's disease. Possibly, therefore, the same high CSF-tau concentrations may be present before the onset of clinical dementia. Follow up studies on such patients will tell whether analysis of CSF-tau is useful as a biochemical marker for early Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Tau and beta-amyloid (1-42) (Abeta42) are two independent markers for the early diagnosis of Alzheimer's disease (AD). In the present study, biochemical markers were validated as tools for differential diagnosis between AD and dementia with Lewy bodies (DLB). Tau, Abeta42 and phospho-tau (181P) were measured in cerebrospinal fluid (CSF) from controls (n=40) and from patients with AD (n=80) or DLB (n=43) using the HT7-AT270 assay (prototype version). In comparison with AD, in DLB no differences were found for Abeta42 and lower phospho-tau. ROC analysis was used to compare the discriminatory power of total tau with that of phospho-tau. The area under the curve (AUC) amounted to 0.782 +/- 0.048 (mean +/- SE) for tau and to 0.839 +/- 0.042 for phospho-tau (p = 0.039) for differentiation of AD from DLB. The present results indicate that CSF phospho-tau may be a good marker for differentiation between AD and DLB. [ABSTRACT FROM AUTHOR]

Abstract: We measured concentrations of Aβ peptides 1–42 and 1–40, and their ratio in plasma of patients carefully categorized clinically and neurochemically as having AD or other dementias with a newly commercially available multiplexing assay, characterized by reasonable laboratory performance (intra-assay imprecision in the range of 1.3–3.8% for Aβ1–42, and 1.8–4.1% for Aβ1–40, inter-assay imprecision for Aβ1–42, Aβ1–40, and Aβ1–42/Aβ1–40 concentration ratio in the range of 2.3–11.5%, 2.2–10.4% and 4.2–9.7%, respectively). Patients with AD or mild cognitive impairment of AD type (MCI-AD) whose clinical diagnosis was supported with CSF biomarkers (n =193) had significantly lower Aβ1–42 plasma concentrations (p <0.007), and Aβ1–42/1–40 ratios (p <0.003) compared to patients with other dementias and MCI of other types (n =64). No significant differences between persons with MCI of AD type and patients with early AD were observed, or between MCI of other types versus patients with early dementia of other types. Our findings reconfirm the hypothesis that alterations of biomarker concentrations occur early in a preclinical AD stage and that these alterations are also reflected in plasma. [Copyright &y& Elsevier]

A significant association between CSF Aβ42 and cognition in patients with Alzheimer’s disease (AD) homozygous for the ∊3 allele of the apolipoprotein E (apoE) has been described. In this study we extended our observations on apoE, as another plaque component, and investigated the association between CSF apoE concentrations and cognitive performance after stratification for the apoE genotype in 62 patients with AD, 19 other forms of dementia and 18 controls. CSF Aβ42 and apoE concentrations were significantly and positively associated with Mini Mental State Examination (MMSE) score in AD (Aβ42: r = 0.332; P = 0.026; apoE: r = 0.386; P = 0.006). For Aβ42 this association was exclusively present in ∊3 homozygotes (r = 0.44; P = 0.014), whereas apoE was correlated with MMSE in ∊4 hetero- or homozygotes subjects (∊4/∊X: r = 0.638; P = 0.004: ∊4/∊4; r = 0.812; P = 0.05). No association was observed between CSF concentrations of Aβ42 and apoE. The significant relationship between MMSE and CSF Aβ42 in ∊3 homozygotes and apoE in ∊4 hetero- and homozygotes respectively may suggest that both proteins may be associated independently from each other with cognitive decline. [Copyright &y& Elsevier]