scholarly journals Neurogranin as Cerebrospinal Fluid Biomarker for Alzheimer Disease: An Assay Comparison Study

2018 ◽  
Vol 64 (6) ◽  
pp. 927-937 ◽  
Author(s):  
Eline A J Willemse ◽  
Ann De Vos ◽  
Elizabeth M Herries ◽  
Ulf Andreasson ◽  
Sebastiaan Engelborghs ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Clinical Performance ◽  
Lewy Bodies ◽  
Analysis Of Covariance ◽  
Group Differences ◽  
Subjective Cognitive Decline ◽  
Terminal Part ◽  
Washington University

Abstract BACKGROUND Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results. METHODS The neurogranin Erenna® assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, Mölndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis. Clinical performance of the 3 assays was compared in samples from individuals diagnosed with subjective cognitive decline (n = 22), and in patients with AD (n = 22), frontotemporal dementia (n = 22), dementia with Lewy bodies (n = 22), or vascular dementia (n = 20), adjusted for sex and age. RESULTS The assays detected different epitopes of neurogranin: the WashU assay detected the N-terminal part of neurogranin (S10-D23) and a C-terminal part (G49-G60), the ADx assay detected C-terminal neurogranin truncated at P75, and the UGot assay detected the C-terminal neurogranin with intact ending (D78). Spearman ρ was 0.95 between ADx and WashU, 0.87 between UGot and WashU, and 0.81 between UGot and ADx. ANCOVA (analysis of covariance) showed group differences for ranked neurogranin concentrations in each assay (all P < 0.05), with specific increases in AD. CONCLUSIONS Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information, at least in the context of neurodegenerative diseases.

Increased Cerebrospinal Fluid Concentration of ZnT3 Is Associated with Cognitive Impairment in Alzheimer’s Disease

2020 ◽  
Vol 77 (3) ◽  
pp. 1143-1155
Author(s):  
Daniela Enache ◽  
Joana B. Pereira ◽  
Vesna Jelic ◽  
Bengt Winblad ◽  
Per Nilsson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Depressive Symptoms ◽  
Cognitive Decline ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Synaptic Proteins ◽  
Subjective Cognitive Decline

Background: Cognitive deficits arising in the course of Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and Parkinson’s disease with dementia (PDD) are directly linked to synaptic loss. Postmortem studies suggest that zinc transporter protein 3 (ZnT3), AMPA glutamate receptor 3 (GluA3), and Dynamin1 are associated with cognitive decline in AD and Lewy body dementia patients. Objective: We aimed to evaluate the diagnostic value of ZnT3, GluA3, and Dynamin 1 in the cerebrospinal fluid (CSF) of patients with dementia due to AD, DLB, and PDD compared to cognitively normal subjective cognitive decline (SCD) patients in a retrospective study. In addition, we assessed the relationship between synaptic markers and age, sex, cognitive impairment, and depressive symptoms as well as CSF amyloid, phosphorylated tau (p-tau), and total tau (T-tau). Methods: Commercially available ELISA immunoassay was used to measure the levels of proteins in a total of 97 CSF samples from AD (N = 24), PDD (N = 18), DLB (N = 27), and SCD (N = 28) patients. Cognitive impairment was assessed using the Mini-Mental State Examination (MMSE). Results: We found a significant increase in the concentrations of ZnT3, GluA3, and Dynamin1 in AD (p = 0.002) and of ZnT3 and Dynamin 1 in DLB (p = 0.001, p = 0.002) when compared to SCD patients. Changes in ZnT3 concentrations correlated with MMSE scores in AD (p = 0.011), and with depressive symptoms in SCD (p = 0.041). Conclusion: We found alteration of CSF levels of synaptic proteins in AD, PDD, and DLB. Our results reveal distinct changes in CSF concentrations of ZnT3 that could reflect cognitive impairment in AD with implications for future prognostic and diagnostic marker development.

scholarly journals Cerebrospinal Fluid Hypocretin and Nightmares in Dementia Syndromes

2021 ◽  
pp. 19-25
Author(s):  
Lynn Marie Trotti ◽  
Donald L. Bliwise ◽  
Glenda L. Keating ◽  
David B. Rye ◽  
William T. Hu
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Cholinesterase Inhibitor ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Cognitively Normal ◽  
Dementia Patients ◽  
Sleep Questionnaires ◽  
Sleep Alterations ◽  
Normal Controls

Background/Aims: Hypocretin promotes wakefulness and modulates REM sleep. Alterations in the hypocretin system are increasingly implicated in dementia. We evaluated relationships among hypocretin, dementia biomarkers, and sleep symptoms in elderly participants, most of whom had dementia. Methods: One-hundred twenty-six adults (mean age 66.2 ± 8.4 years) were recruited from the Emory Cognitive Clinic. Diagnoses were Alzheimer disease (AD; n = 60), frontotemporal dementia (FTD; n = 21), and dementia with Lewy bodies (DLB; n = 20). We also included cognitively normal controls (n = 25). Participants and/or caregivers completed sleep questionnaires and lumbar puncture was performed for cerebrospinal fluid (CSF) assessments. Results: Except for sleepiness (worst in DLB) and nocturia (worse in DLB and FTD) sleep symptoms did not differ by diagnosis. CSF hypocretin concentrations were available for 87 participants and normal in 70, intermediate in 16, and low in 1. Hypocretin levels did not differ by diagnosis. Hypocretin levels correlated with CSF total τ levels only in men (r = 0.34; p = 0.02). Lower hypocretin levels were related to frequency of nightmares (203.9 ± 29.8 pg/mL in those with frequent nightmares vs. 240.4 ± 46.1 pg/mL in those without; p = 0.05) and vivid dreams (209.1 ± 28.3 vs. 239.5 ± 47.8 pg/mL; p = 0.014). Cholinesterase inhibitor use was not associated with nightmares or vivid dreaming. Conclusion: Hypocretin levels did not distinguish between dementia syndromes. Disturbing dreams in dementia patients may be related to lower hypocretin concentrations in CSF.

scholarly journals VGF Peptides in Cerebrospinal Fluid of Patients with Dementia with Lewy Bodies

2019 ◽  
Vol 20 (19) ◽  
pp. 4674 ◽  
Author(s):  
Inger van Steenoven ◽  
Barbara Noli ◽  
Cristina Cocco ◽  
Gian-Luca Ferri ◽  
Patrick Oeckl ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Analytical Methods ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Disease Stage ◽  
Selected Reaction Monitoring ◽  
Csf Biomarkers ◽  
Potential Biomarker ◽  
Proteomic Study

In a previous proteomic study, we identified the neurosecretory protein VGF (VGF) as a potential biomarker for dementia with Lewy bodies (DLB). Here, we extended the study of VGF by comparing levels in cerebrospinal fluid (CSF) from 44 DLB patients, 20 Alzheimer’s disease (AD) patients, and 22 cognitively normal controls selected from the Amsterdam Dementia Cohort. CSF was analyzed using two orthogonal analytical methods: (1) In-house-developed quantitative ELISA and (2) selected reaction monitoring (SRM). We further addressed associations of VGF with other CSF biomarkers and cognition. VGF levels were lower in CSF from patients with DLB compared to either AD patients or controls. VGF was positively correlated with CSF tau and α-synuclein (0.55 < r < 0.75), but not with Aβ1-42. In DLB patients, low VGF levels were related to a more advanced cognitive decline at time of first presentation, whereas high levels of VGF were associated with steeper subsequent longitudinal cognitive decline. Hence, CSF VGF levels were lower in DLB compared to both AD and controls across different analytical methods. The strong associations with cognitive decline further points out VGF as a possible disease stage or prognostic marker for DLB.

[P3-297]: SUBJECTIVE COGNITIVE DECLINE AND NEUROIMAGING AND CEREBROSPINAL FLUID MARKERS OF CEREBROVASCULAR HEALTH: THE VANDERBILT MEMORY AND AGING PROJECT

2017 ◽  
Vol 13 (7S_Part_22) ◽  
pp. P1057-P1058
Author(s):  
Katherine A. Gifford ◽  
Faizan Badami ◽  
Timothy J. Hohman ◽  
Elizabeth E. Moore ◽  
Kimberly R. Pechman ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Subjective Cognitive Decline ◽  
Cerebrovascular Health

scholarly journals Kynurenic Acid Levels in Cerebrospinal Fluid from Patients with Alzheimer's Disease or Dementia with Lewy Bodies

2014 ◽  
Vol 7 ◽  
pp. IJTR.S13958 ◽  
Author(s):  
Malin Wennström ◽  
Henrietta M Nielsen ◽  
Funda Orhan ◽  
Elisabet Londos ◽  
Lennart Minthon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Decline ◽  
Cognitive Functions ◽  
Dementia With Lewy Bodies ◽  
Kynurenic Acid ◽  
Lewy Bodies ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1

Kynurenic acid (KYNA) is implicated in cognitive functions. Altered concentrations of the compound are found in serum and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). Further studies to determine whether KYNA serves as a biomarker for cognitive decline and dementia progression are required. In this study, we measured CSF KYNA levels in AD patients (n = 19), patients with dementia with Lewy bodies (DLB) (n = 18), and healthy age-matched controls (Ctrls)) (n = 20) to further explore possible correlations between KYNA levels, cognitive decline, and well-established AD and inflammatory markers. Neither DLB patients nor AD patients showed significantly altered CSF KYNA levels compared to Ctrls. However, female AD patients displayed significantly higher KYNA levels compared to male AD patients, a gender difference not seen in the Ctrl or DLB group. Levels of KYNA significantly correlated with the AD-biomarker P-tau and the inflammation marker soluble intercellular adhesion molecule-1 (sICAM-1) in the AD patient group. No associations between KYNA and cognitive functions were found. Our study shows that, although KYNA was not associated with cognitive decline in AD or DLB patients, it may be implicated in AD-related hyperphosphorylation of tau and inflammation. Further studies on larger patient cohorts are required to understand the potential role of KYNA in AD and DLB.

Subjective Cognitive Impairment and Mild Cognitive Impairment (Predementias)

2017 ◽  
Author(s):  
Shashank Beesam ◽  
George Grossberg ◽  
Eric Marin
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Treatment Modalities ◽  
Subjective Cognitive Decline ◽  
Neurocognitive Disorder ◽  
Subjective Cognitive Impairment ◽  
Individualized Care ◽  
Age Related

Alzheimer disease is thought to have an insidious progression, with asymptomatic brain changes occurring decades prior to formal diagnosis. In recent years, efforts have been made to identify and characterize these changes into a spectrum beginning with subjective cognitive decline through the development of major neurocognitive disorder. Through this process, progress has been made into the predictive factors, prevention, and treatment modalities for the various stages of cognitive decline. In addition to pharmacologic therapies, studies have shown the value in physical, mental, social, and spiritual activity combined with support from physicians, family, and caregivers. Furthermore, individualized care, open and honest physician-patient dialogue, and emphasis on lifestyle modifications have been shown to achieve optimal quality of life and may also decrease the rate of cognitive decline. This review contains 5 figures, 5 tables, and 36 references. Key words: age-related cognitive decline, Alzheimer disease, major neurocognitive disorder, mild cognitive impairment, mild neurocognitive disorder, senior moment, subjective cognitive impairment

scholarly journals Multiplexed Proteomic Analysis of Oxidation and Concentrations of Cerebrospinal Fluid Proteins in Alzheimer Disease

2007 ◽  
Vol 53 (4) ◽  
pp. 657-665 ◽  
Author(s):  
Minna A Korolainen ◽  
Tuula A Nyman ◽  
Paula Nyyssönen ◽  
E Samuel Hartikainen ◽  
Tuula Pirttilä
Keyword(s):  
Oxidative Stress ◽  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Cognitive Decline ◽  
Oxidative Modification ◽  
Cerebrospinal Fluid Proteins ◽  
Age Related ◽  
Aging Women ◽  
Specific Proteins ◽  
Brain Specific Proteins

Abstract Background: Carbonylation is an irreversible oxidative modification of proteins that has been linked to various conditions of oxidative stress, aging, physiological disorders, and disease. Increased oxidative stress is thus also considered to play a role in the pathogenesis of age-related neurodegenerative disorders such as Alzheimer disease (AD). In addition, it has recently become evident that the response mechanisms to increased oxidative stress may depend on sex. Several oxidized carbonylated proteins have been identified in plasma and brain of AD patients by use of 2-dimensional oxyblotting. Methods: In this pilot study, we estimated the concentrations and carbonylation of the most abundant cerebrospinal fluid proteins in aging women and men, both AD patients suffering from mild dementia and individuals exhibiting no cognitive decline. Oxidized carbonylated proteins were analyzed with 2-dimensional multiplexed oxyblotting, mass spectrometry, and database searches. Results: Signals for β-trace, λ chain, and transthyretins were decreased in probable AD patients compared with controls. The only identified protein exhibiting an increased degree of carbonylation in AD patients was λ chain. The concentrations of proteins did not generally differ between men and women; however, vitamin D–binding protein, apolipoprotein A-I, and α-1-antitrypsin exhibited higher extents of carbonylation in men. Conclusions: None of the brain-specific proteins exhibited carbonylation changes in probable AD patients compared with age-matched neurological controls showing no cognitive decline. The carbonylation status of proteins differed between women and men. Two-dimensional multiplexed oxyblotting is applicable to study both the concentrations and carbonylation of cerebrospinal fluid proteins.

scholarly journals Cerebrospinal Fluid Markers in Dementia With Lewy Bodies Compared With Alzheimer Disease

2003 ◽  
Vol 60 (9) ◽  
Author(s):  
Estrella Gómez-Tortosa ◽  
Isabel Gonzalo ◽  
Samira Fanjul ◽  
Maria José Sainz ◽  
Susana Cantarero ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Alzheimer Disease ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies
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