Cerebrospinal Fluid pH and Monoamine and Glucolytic Metabolites in Alzheimer's Disease

1974 ◽  
Vol 124 (580) ◽  
pp. 280-287 ◽  
Author(s):  
C. G. Gottfries ◽  
Åke Kjällquist ◽  
Urban Pontén ◽  
B. E. Roos ◽  
G. Sundbärg

Determinations of acid monoamine metabolites, such as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), in cerebrospinal fluid (CSF) give valid information on the metabolism of the corresponding amines in the brain tissue (Moir et al., 1970; Roos, 1970). The monoamine metabolites in the CSF are related to age. The concentrations of HVA and 5-HIAA increase with age (Gottfries et al., 1971). Probenecid blocks the elimination of HVA and 5-HIAA from brain tissue to blood (Neff et al., 1964, 1967; Werdinius, 1966) and from CSF to blood (Guldberg et al., 1966; Olsson and Roos, 1968). Probenecid thus normally induces an increase in the concentrations of the acid monoamine metabolites in the CSF, which is related to the turnover of monoamines in the brain tissue.

2013 ◽  
Vol 275 (4) ◽  
pp. 418-427 ◽  
Author(s):  
X. Li ◽  
T.-Q. Li ◽  
N. Andreasen ◽  
M. K. Wiberg ◽  
E. Westman ◽  
...  

2018 ◽  
Vol 12 ◽  
Author(s):  
Simin Mahinrad ◽  
Marjolein Bulk ◽  
Isabelle van der Velpen ◽  
Ahmed Mahfouz ◽  
Willeke van Roon-Mom ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Shorena Janelidze ◽  
Erik Stomrud ◽  
Ruben Smith ◽  
Sebastian Palmqvist ◽  
Niklas Mattsson ◽  
...  

AbstractCerebrospinal fluid (CSF) p-tau181 (tau phosphorylated at threonine 181) is an established biomarker of Alzheimer’s disease (AD), reflecting abnormal tau metabolism in the brain. Here we investigate the performance of CSF p-tau217 as a biomarker of AD in comparison to p-tau181. In the Swedish BioFINDER cohort (n = 194), p-tau217 shows stronger correlations with the tau positron emission tomography (PET) tracer [18F]flortaucipir, and more accurately identifies individuals with abnormally increased [18F]flortaucipir retention. Furthermore, longitudinal increases in p-tau217 are higher compared to p-tau181 and better correlate with [18F]flortaucipir uptake. P-tau217 correlates better than p-tau181 with CSF and PET measures of neocortical amyloid-β burden and more accurately distinguishes AD dementia from non-AD neurodegenerative disorders. Higher correlations between p-tau217 and [18F]flortaucipir are corroborated in an independent EXPEDITION3 trial cohort (n = 32). The main results are validated using a different p-tau217 immunoassay. These findings suggest that p-tau217 might be more useful than p-tau181 in the diagnostic work up of AD.


2019 ◽  
Vol 1124 ◽  
pp. 165-172
Author(s):  
Daniela Delfino ◽  
Diana Valeria Rossetti ◽  
Claudia Martelli ◽  
Ilaria Inserra ◽  
Federica Vincenzoni ◽  
...  

2020 ◽  
Vol 6 (43) ◽  
pp. eaaz9360 ◽  
Author(s):  
Lenora Higginbotham ◽  
Lingyan Ping ◽  
Eric B. Dammer ◽  
Duc M. Duong ◽  
Maotian Zhou ◽  
...  

Alzheimer’s disease (AD) lacks protein biomarkers reflective of its diverse underlying pathophysiology, hindering diagnostic and therapeutic advancements. Here, we used integrative proteomics to identify cerebrospinal fluid (CSF) biomarkers representing a wide spectrum of AD pathophysiology. Multiplex mass spectrometry identified ~3500 and ~12,000 proteins in AD CSF and brain, respectively. Network analysis of the brain proteome resolved 44 biologically diverse modules, 15 of which overlapped with the CSF proteome. CSF AD markers in these overlapping modules were collapsed into five protein panels representing distinct pathophysiological processes. Synaptic and metabolic panels were decreased in AD brain but increased in CSF, while glial-enriched myelination and immunity panels were increased in brain and CSF. The consistency and disease specificity of panel changes were confirmed in >500 additional CSF samples. These panels also identified biological subpopulations within asymptomatic AD. Overall, these results are a promising step toward a network-based biomarker tool for AD clinical applications.


2020 ◽  
Vol 28 (1) ◽  
pp. 19-52 ◽  
Author(s):  
Renu Chandra Segaran ◽  
Li Yun Chan ◽  
Hong Wang ◽  
Gautam Sethi ◽  
Feng Ru Tang

Radiation exposure may induce Alzheimer's disease (AD), depression or schizophrenia. A number of experimental and clinical studies suggest the involvement of miRNA in the development of these diseases, and also in the neuropathological changes after brain radiation exposure. The current literature review indicated the involvement of 65 miRNAs in neuronal development in the brain. In the brain tissue, blood, or cerebral spinal fluid (CSF), 11, 55, or 28 miRNAs are involved in the development of AD respectively, 89, 50, 19 miRNAs in depression, and 102, 35, 8 miRNAs in schizophrenia. We compared miRNAs regulating neuronal development to those involved in the genesis of AD, depression and schizophrenia and also those driving radiation-induced brain neuropathological changes by reviewing the available data. We found that 3, 11, or 8 neuronal developmentrelated miRNAs from the brain tissue, 13, 16 or 14 miRNAs from the blood of patient with AD, depression and schizophrenia respectively were also involved in radiation-induced brain pathological changes, suggesting a possibly specific involvement of these miRNAs in radiation-induced development of AD, depression and schizophrenia respectively. On the other hand, we noted that radiationinduced changes of two miRNAs, i.e., miR-132, miR-29 in the brain tissue, three miRNAs, i.e., miR- 29c-5p, miR-106b-5p, miR-34a-5p in the blood were also involved in the development of AD, depression and schizophrenia, thereby suggesting that these miRNAs may be involved in the common brain neuropathological changes, such as impairment of neurogenesis and reduced learning memory ability observed in these three diseases and also after radiation exposure.


2021 ◽  
pp. 1-14
Author(s):  
Christiana Bjorkli ◽  
Claire Louet ◽  
Trude Helen Flo ◽  
Mary Hemler ◽  
Axel Sandvig ◽  
...  

Background: Preclinical models of Alzheimer’s disease (AD) can provide valuable insights into the onset and progression of the disease, such as changes in concentrations of amyloid-β (Aβ) and tau in cerebrospinal fluid (CSF). However, such models are currently underutilized due to limited advancement in techniques that allow for longitudinal CSF monitoring. Objective: An elegant way to understand the biochemical environment in the diseased brain is intracerebral microdialysis, a method that has until now been limited to short-term observations, or snapshots, of the brain microenvironment. Here we draw upon patient-based findings to characterize CSF biomarkers in a commonly used preclinical mouse model for AD. Methods: Our modified push-pull microdialysis method was first validated ex vivo with human CSF samples, and then in vivo in an AD mouse model, permitting assessment of dynamic changes of CSF Aβ and tau and allowing for better translational understanding of CSF biomarkers. Results: We demonstrate that CSF biomarker changes in preclinical models capture what is observed in the brain; with a decrease in CSF Aβ observed when plaques are deposited, and an increase in CSF tau once tau pathology is present in the brain parenchyma. We found that a high molecular weight cut-off membrane allowed for simultaneous sampling of Aβ and tau, comparable to CSF collection by lumbar puncture in patients. Conclusion: Our approach can further advance AD and other neurodegenerative research by following evolving neuropathology along the disease cascade via consecutive sampling from the same animal and can additionally be used to administer pharmaceutical compounds and assess their efficacy (Bjorkli, unpublished data).


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