Decreased cerebrospinal fluid amyloid β 38, 40, 42, and 43 levels in sporadic and hereditary cerebral amyloid angiopathy

ObjectiveVascular amyloid β (Aβ) accumulation is the hallmark of cerebral amyloid angiopathy (CAA). The composition of cerebrospinal fluid (CSF) of CAA patients may serve as a diagnostic biomarker of CAA. We studied the diagnostic potential of the peptides Aβ38, Aβ40, Aβ42, and Aβ43 in patients with sporadic CAA (sCAA), hereditary Dutch-type CAA (D-CAA), and Alzheimer disease (AD).MethodsAβ peptides were quantified by immunoassays in a discovery group (26 patients with sCAA and 40 controls), a validation group (40 patients with sCAA, 40 patients with AD, and 37 controls), and a group of 22 patients with D-CAA and 54 controls. To determine the diagnostic accuracy, the area under the curve (AUC) was calculated using a receiver operating characteristic curve with 95% confidence interval (CI).ResultsWe found decreased levels of all Aβ peptides in sCAA patients and D-CAA patients compared to controls. The difference was most prominent for Aβ42 (AUC of sCAA vs controls for discovery: 0.90, 95% CI = 0.82–0.99; for validation: 0.94, 95% CI = 0.89–0.99) and Aβ43 (AUC of sCAA vs controls for discovery: 0.95, 95% CI = 0.88–1.00; for validation: 0.91, 95% CI = 0.83–1.0). All Aβ peptides except Aβ43 were also decreased in sCAA compared to AD (CSF Aβ38: AUC = 0.82, 95% CI = 0.71–0.93; CSF Aβ40: AUC = 0.88, 95% CI = 0.80–0.96; CSF Aβ42: AUC = 0.79, 95% CI = 0.66–0.92).Paroxysmal Cerebral Disorder

Diagnosis of progressive supranuclear palsy: can measurement of tau forms help?

Item does not contain fulltextRecently, a new assay for the differential diagnosis of progressive supranuclear palsy (PSP) was proposed. It was shown that the ratio of 33/55 kDa tau forms in cerebrospinal fluid (CSF) was specifically reduced in PSP CSF. We aimed to reproduce these results, but were not able to detect the tau forms in CSF. We demonstrate that i) CSF total tau levels are too low to be detected by the published protocol, and ii) the described 33 and 55 kDa bands are likely the heavy and light chains of IgG used in the assay. We conclude that more sensitive techniques are needed to measure tau forms in CSF.1 januari 201

Do amyloid beta-associated factors co-deposit with Abeta in mouse models for Alzheimer's disease?

Contains fulltext : 88845.pdf (publisher's version ) (Open Access)Senile plaques and cerebral amyloid angiopathy in Alzheimer's disease (AD) patients not only consist of the amyloid-beta protein (Abeta), but also contain many different Abeta-associated factors, such as heparan sulfate proteoglycans, apolipoproteins, and complement factors. These factors may all influence Abeta deposition, aggregation, and clearance and therefore seem important in the development of human Abeta deposits. To study AD pathology and test new therapeutic agents, many different mouse models have been created. By transgenic expression of the amyloid-beta protein precursor, frequently in combination with other transgenes, these animals develop Abeta deposits that morphologically resemble their human counterparts. Whether this resemblance also applies to the presence of Abeta-associated factors is largely unclear. In this review, the co-deposition of factors known to associate with human Abeta deposits is summarized for several different AD mouse models

A multifunctional ELISA to measure proteins: oxPin1 in Alzheimer's brain as an example

Contains fulltext : 152150.pdf (publisher's version ) (Open Access)Publisher: Abstract available from the publisher. Du

Detection of tau forms in CSF requires sensitive techniques.

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Optimisation of the quantification of glutamine synthetase and myelin basic protein in cerebrospinal fluid by a combined acidification and neutralisation protocol.

Item does not contain fulltextThe measurement of proteins in cerebrospinal fluid (CSF) by enzyme-linked immunosorbent assays (ELISAs) is becoming increasingly important in the diagnosis of many neurodegenerative diseases such as Alzheimer's Disease. However, detection of proteins in these immunoassays can be hampered by confounding factors either present in the sample matrix or inherent to the protein of interest. These confounding factors may, for example, include protein aggregation or binding to other proteins resulting in epitope masking. Furthermore, the pH of CSF may vary considerably amongst different samples which may limit standardisation of CSF analysis. Pre-treatment of CSF to liberate epitopes or optimise conditions for antibody binding may enhance protein detection. In the current study we investigated whether CSF acidification followed by neutralisation (in short: AFBN) or neutralisation alone prior to measurement might improve the detection of a panel of brain-specific proteins. We demonstrate that the AFBN pre-treatment protocol for CSF significantly enhances the measurement of glutamine synthetase (GS) and myelin basic protein (MBP) in CSF but does not affect detection of glial fibrillary protein (GFAP), amyloid beta 42 (Abeta(4)(2)), total tau (t-tau) or phosphorylated tau (p-tau). Neutralisation alone did not improve detection of any of the proteins tested. Based on our results, we suggest including the AFBN protocol in the evaluation of new biomarker development protocols to avoid confounders such as CSF pH or epitope-masking of the target protein

Methods for analysis of amyloid-beta aggregates.

Item does not contain fulltextAmyloid-beta protein (Abeta) accumulation is one of the major hallmarks of Alzheimer's disease and plays a crucial role in its pathogenesis. Abeta aggregates into fibrils, but rather than these end-products of the aggregation process, intermediate species, referred to as oligomers, have been identified as the most neurotoxic Abeta aggregates. To characterize the different Abeta species and to study the aggregation process, a wide range of techniques has been applied over the past years. These techniques aim to visualize the different Abeta species and study their structure, to separate them, and to quantify the aggregated Abeta forms by immunology-based methods. In this review, we provide an overview and discussion of the most important techniques used for these aims. Often a combination of techniques will be appropriate to obtain the most optimal information

Detection of elevated levels of alpha-synuclein oligomers in CSF from patients with Parkinson disease

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Cerebrospinal Fluid NrCAM is not a Suitable Biomarker to Discriminate between Dementia Disorders - A Pilot Study

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The Diagnostic Value of CSF Amyloid-beta43 in Differentiation of Dementia Syndromes

Item does not contain fulltextAmyloid-beta (Abeta) is known as the most prominent core protein in Alzheimer's Disease (AD) senile plaques. Although research has focused mainly on Abeta40 and Abeta42 as potential cerebrospinal fluid (CSF) biomarkers, a range of Abeta peptides with variable lengths has been demonstrated in the brains and CSF of AD patients. Recently, it has been found that the Abeta43 peptide may be more abundant than previously assumed, could therefore play an important role in AD pathophysiology, and hence also function as putative biomarker. In this study the value of CSF Abeta43 in AD diagnosis was investigated. Abeta43 levels in CSF were highly correlated with Abeta42 levels. Furthermore, in differentiation of AD from nondemented controls and from patients with Lewy body dementia and frontotemporal dementia, Abeta43 had an equal diagnostic value as Abeta42, both as a single biomarker and in combination with total and phosphorylated tau. In conclusion, quantification of Abeta43 in CSF does not add novel diagnostic information to the differential diagnosis of AD compared to existing biomarkers