Identification of synaptic vesicle, pre- and postsynaptic proteins in human cerebrospinal fluid using liquid-phase isoelectric focusing

Davidsson, Pia; Puchades, Maja; Blennow, Kaj

doi:10.1002/(sici)1522-2683(19990301)20:3<431::aid-elps431>3.0.co;2-2

Cited by 82 publications

(17 citation statements)

References 52 publications

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“…Several pre-and postsynaptic proteins have been identified in CSF using a procedure based on protein precipitation followed by liquid-phase isoelectric focusing and western blotting. These proteins include rab3a, synaptotagmin, growthassociated protein (GAP-43), synaptosomalassociated protein (SNAP-25), and neurogranin (Davidsson et al 1999). An immunoassay for GAP-43 showed that CSF levels are higher in AD patients than in controls and patients with frontotemporal dementia (Sjogren et al 2001b).…”

Section: Neuronal and Synaptic Degenerationmentioning

confidence: 99%

Fluid Biomarkers in Alzheimer Disease

Blennow

Zetterberg

Fagan

2012

Cold Spring Harbor Perspectives in Medicine

176

148

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Research progress has provided detailed understanding of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new drug candidates with putative disease-modifying effects, which are now being tested in clinical trials. The promise of effective therapy has created a great need for biomarkers able to detect AD in the predementia phase, because drugs will probably be effective only if neurodegeneration is not too advanced. In this chapter, cerebrospinal fluid (CSF) and plasma biomarkers are reviewed. The core CSF biomarkers total tau (T-tau), phosphorylated tau (P-tau) and the 42 amino acid form of b-amyloid (Ab42) reflect AD pathology, and have high diagnostic accuracy to diagnose AD with dementia and prodromal AD in mild cognitive impairment cases. The rationale for the use of CSF biomarkers to identify and monitor the mechanism of action of new drug candidates is also outlined in this chapter.

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Section: Neuronal and Synaptic Degenerationmentioning

confidence: 99%

Fluid Biomarkers in Alzheimer Disease

Blennow

Zetterberg

Fagan

2012

Cold Spring Harbor Perspectives in Medicine

176

148

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“…135,136 GAP43 protein levels are decreased in the frontal cortex and the hippocampus in AD. [137][138][139] GAP43 is secreted to the CSF at which it serves as a potential marker for synaptic degeneration or plasticity. 139 In AD, increased CSF levels of GAP43 are found, although CSF GAP43 is normal in FTD and in PD.…”

Section: Gap43 (Neuromodulin)mentioning

confidence: 99%

“…[137][138][139] GAP43 is secreted to the CSF at which it serves as a potential marker for synaptic degeneration or plasticity. 139 In AD, increased CSF levels of GAP43 are found, although CSF GAP43 is normal in FTD and in PD. 50,69,140 There is a clear correlation between the CSF levels of T-tau and GAP 50,69 and some data suggest that the ratio of CSF GAP43/T-tau may be of diagnostic importance.…”

Section: Gap43 (Neuromodulin)mentioning

confidence: 99%

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

2004

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Summary:The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has made patients seek medical advice at an earlier stage of the disease. This has highlighted the importance of diagnostic markers for early AD. However, there is no clinical method to determine which of the patients with mild cognitive impairment (MCI) will progress to AD with dementia, and which have a benign form of MCI without progression. In this paper, the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is reviewed. The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of ␤-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson's disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia. Early diagnosis of AD is not only of importance to be able to initiate symptomatic treatment with AChE inhibitors, but will be the basis for initiation of treatment with drugs aimed at slowing down or arresting the degenerative process, such as ␥-secretase inhibitors, if these prove to affect AD pathology and to have a clinical effect.

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“…There are several reports about the efflux of these antigens into peripheral lymphoid organs and their ability to initiate a significant humoral response [1,2,7]. CSF drains mostly into the blood, deep cervical lymph nodes and lymphatics located in the connective tissue sheaths of the peripheral nervous system [1,2], and partly drains into fluid spaces lying along the spinal nerve roots and peripheral nerves [3,4,18]. Thus, intracerebrally injected soluble protein antigens are known to drain into the cervical lymph nodes and initiate antigen-specific immune responses [12].…”

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confidence: 99%

Comparison of Antibody Titers in Rabbits Following Immunization with Inactivated Influenza Virus via Subarachnoidal or Subcutaneous Route

Shin

Sakoda

Kim

et al. 2007

The Journal of Veterinary Medical Science

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ABSTRACT. Rabbits were immunized with inactivated influenza virus via the subarachnoidal (SA) or subcutaneous (SC) route, and the antibody titers in cerebrospinal fluid (CSF) and serum were assayed. There were no nervous signs or morphological lesions related to SA immunization. In the SC group, the antibody titer was elevated in serum, but not elevated in CSF. In the SA group, the antibody titer was significantly elevated in serum and even in CSF, and their antibody titers were much greater than in the SC group. The present results suggest that intrathecal immunization is more effective than SC immunization at inducing a protective immune response against the transneural spread of viruses. [13,14,16,21]. Also, Yao et al. [25] reported that encephalitis was observed within 3-5 days after the intranasal infection of new mice with A/Aichi/ 2/68 INFV (H3N2) strain. The CNS and peripheral nerves are protected from impact by cerebrospinal fluid (CSF) [18]. The CNS is an immunologically privileged site and serum antibody does not influx into CSF under normal conditions due to blood-brain barrier (BBB) [7,12]; therefore, those neurotropic infectious agents may not meet the antibody response after they invade the nervous tissue. Serum antibody is effective after the pathogens are elicited on inflammation, which increases BBB permeability.Direct inoculation of antigens into CSF caused intrathecal immunization. We have previously shown that intrathecal immunization with inactivated pseudorabies virus, a neurotropic virus, completely protected the animals against lethal virus challenge, whereas all non-immunized and several subcutaneously immunized mice died after developing neurological signs [20]. Previous reports have shown that immunization via the brain or CSF elicits systemic humoral immune responses in the cervical lymph nodes, spleen, serum and CSF [7,8,19]. Furthermore, antigens are more immunogenic when administered into CNS than into conventional extracerebral sites. When CSF and serum antibody responses to albumin, which was administered into CSF or muscle, were compared with respect to the antibody titer in a rat model with normal BBB function, the CSF/ serum titer ratio and the ratio of immunoglobulin G subclasses were both elevated more prominently following CSF administration than intramuscular inoculation [1,2,7]. In this study, we compared the magnitude of the antibody responses in serum and CSF to inactivated INFV following immunization via the subarachnoidal (SA) or subcutaneous (SC) route, and examined the pathological effects of SA inoculation of INFV antigens in the brain.INFV, A/Aichi/2/68 INFV (H3N2) strain, was propagated in allantoic fluid of 10 day-old embryonated chicken eggs at 35°C for 48 hr. Virus was concentrated and purified by high-speed centrifugation, passed through a 10-50% sucrose density gradient, and resuspended in phosphatebuffered saline (PBS). For formalin-inactivated virus vaccines, the purified viruses were treated with 0.1% formalin at 4°C for a week. Protein concentrations o...

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Identification of synaptic vesicle, pre- and postsynaptic proteins in human cerebrospinal fluid using liquid-phase isoelectric focusing

Cited by 82 publications

References 52 publications

Fluid Biomarkers in Alzheimer Disease

Fluid Biomarkers in Alzheimer Disease

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

Comparison of Antibody Titers in Rabbits Following Immunization with Inactivated Influenza Virus via Subarachnoidal or Subcutaneous Route

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