scholarly journals Potential Fluid Biomarkers for the Diagnosis of Mild Cognitive Impairment

2019 ◽  
Vol 20 (17) ◽  
pp. 4149 ◽  
Author(s):  
Vo Van Giau ◽  
Eva Bagyinszky ◽  
Seong Soo A. An
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Phosphorylated Tau ◽  
Transitional State ◽  
Total Tau ◽  
Current State ◽  
Risk Of Progression ◽  
Csf Levels ◽  
Potential Fluid

Mild cognitive impairment (MCI) is characterized by a level of cognitive impairment that is lower than normal for a person’s age, but a higher function than that that observed in a demented person. MCI represents a transitional state between normal aging and dementia disorders, especially Alzheimer’s disease (AD). Much effort has been made towards determining the prognosis of a person with MCI who will convert to AD. It is now clear that cerebrospinal fluid (CSF) levels of Aβ40, Aβ42, total tau and phosphorylated tau are useful for predicting the risk of progression from MCI to AD. This review highlights the advantages of the current blood-based biomarkers in MCI, and discusses some of these challenges, with an emphasis on recent studies to provide an overview of the current state of MCI.

O5-04-05: Aerobic exercise reduces phosphorylated tau protein in cerebrospinal fluid in older adults with mild cognitive impairment

2015 ◽  
Vol 11 (7S_Part_7) ◽  
pp. P324-P324 ◽  
Author(s):  
Laura D. Baker ◽  
Jeannine S. Skinner ◽  
Suzanne Craft ◽  
Kaycee M. Sink ◽  
Thomas Montine ◽  
...  
Keyword(s):  
Older Adults ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Aerobic Exercise ◽  
Tau Protein ◽  
Phosphorylated Tau ◽  
Phosphorylated Tau Protein

The Head Turning Sign in Dementia and Mild Cognitive Impairment: Its Relationship to Cognition, Behavior, and Cerebrospinal Fluid Biomarkers

2018 ◽  
Vol 46 (1-2) ◽  
pp. 42-49 ◽  
Author(s):  
João Durães ◽  
Miguel Tábuas-Pereira ◽  
Rui Araújo ◽  
Diana Duro ◽  
Inês Baldeiras ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Tau Proteins ◽  
Cognitive Measures ◽  
Head Turning ◽  
Total Tau ◽  
Scale Scores

Background/Aims: The head turning sign (HTS) is frequently noticed in clinical practice, but few studies have investigated its etiological and neuropsychological correlates. Methods: The presence and frequency of the HTS was operationalized and prospectively evaluated in patients with Alzheimer’s disease (AD), amnestic mild cognitive impairment (MCI), and behavioral-variant frontotemporal dementia (bvFTD). Cerebrospinal fluid (CSF) samples for AD biomarkers were collected. Mini-Mental State Examination, Montreal Cognitive Assessment, Geriatric Depression Scale (GDS), and insight scale scores were ascertained. Results: A total of 84 patients were included. The HTS was more prevalent in AD than in MCI or bvFTD. It correlated negatively with cognitive measures and depression. It also had a positive correlation with CSF total tau and hyperphosphorylated tau proteins. Total tau protein and GDS score were the only variables independently associated with the HTS. Conclusions: The presence of the HTS in a cognitively impaired individual suggests a diagnosis of AD. A higher HTS frequency correlates with higher CSF total tau levels, a smaller GDS score, and worse cognitive measures. In the MCI subgroup, the HTS may suggest a higher risk of progression.

scholarly journals Evidence for Elevated Cerebrospinal Fluid ERK1/2 Levels in Alzheimer Dementia

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Philipp Spitzer ◽  
Heinke Schieb ◽  
Heike Kamrowski-Kruck ◽  
Markus Otto ◽  
Davide Chiasserini ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Mitogen Activated Protein Kinase ◽  
Fluid Sample ◽  
Alzheimer Dementia ◽  
Extracellular Signal Regulated Kinase ◽  
Total Tau ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Cerebrospinal fluid (CSF) samples from 33 patients with Alzheimer dementia (AD), 21 patients with mild cognitive impairment who converted to AD during followup (MCI-AD), 25 patients with stable mild cognitive impairment (MCI-stable), and 16 nondemented subjects (ND) were analyzed with a chemiluminescence immunoassay to assess the levels of the mitogen-activated protein kinase ERK1/2 (extracellular signal-regulated kinase 1/2). The results were evaluated in relation to total Tau (tTau), phosphorylated Tau (pTau), and beta-amyloid 42 peptide (Aβ42). CSF-ERK1/2 was significantly increased in the AD group as compared to stable MCI patients and the ND group. Western blot analysis of a pooled cerebrospinal fluid sample revealed that both isoforms, ERK1 and ERK2, and low amounts of doubly phosphorylated ERK2 were detectable. As a predictive diagnostic AD biomarker, CSF-ERK1/2 was inferior to tTau, pTau, and Aβ42.

scholarly journals Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment

2010 ◽  
Vol 32 (3) ◽  
pp. 216-222 ◽  
Author(s):  
Orestes V. Forlenza ◽  
Breno S. Diniz ◽  
Leda L. Talib ◽  
Marcia Radanovic ◽  
Monica S. Yassuda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Total Tau ◽  
Cerebrospinal Fluid Biomarkers ◽  
Antidementia Drugs ◽  
Beta Peptide

OBJECTIVE: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. METHOD: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. RESULTS: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during follow-up (odds ratio = 4.5, CI95% [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ42, p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. DISCUSSION: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease.

scholarly journals Influence of APOE Genotype on Alzheimer’s Disease CSF Biomarkers in a Spanish Population

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
J. A. Monge-Argilés ◽  
R. Gasparini-Berenguer ◽  
M. Gutierrez-Agulló ◽  
C. Muñoz-Ruiz ◽  
J. Sánchez-Payá ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apoe Genotype ◽  
Amnestic Mild Cognitive Impairment ◽  
Spanish Population ◽  
Csf Biomarkers ◽  
Csf Levels

Objectives. To evaluate the association between apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) levels of Alzheimer’s disease (AD) biomarkers and to study the influence of APOE genotype on the development of AD in a Spanish population.Material and Methods. The study comprised 29 amnestic mild cognitive impairment (MCI) patients and 27 control subjects. Using ELISA methodology, CSF biomarkers and tau/Aβratios were obtained. ANOVA and adjusted odds ratios were calculated.Results. We observed the effect of APOE genotype and age on CSF AD variables. The progression to AD was more clearly influenced by CSF AD variables than by age or APOE status.Conclusions. APOE status influences CSF AD variables. However, the presence of APOEε4 does not appear to be a deterministic factor for the development of AD, because CSF variables have a greater influence on progression to the disease. These results confirm previous observations and, to our knowledge, are the first published in a Spanish population.

scholarly journals Amino-Truncated β-Amyloid42 Peptides in Cerebrospinal Fluid and Prediction of Progression of Mild Cognitive Impairment

2005 ◽  
Vol 51 (9) ◽  
pp. 1650-1660 ◽  
Author(s):  
Hugo Vanderstichele ◽  
Geert De Meyer ◽  
Niels Andreasen ◽  
Vesna Kostanjevecki ◽  
Anders Wallin ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Clinical Diagnosis ◽  
Amino Terminus ◽  
Roc Curve Analysis ◽  
Combined Use ◽  
Risk Of Progression ◽  
Discriminant Ability ◽  
Aβ42 Peptide

Abstract Background: Early identification of patients with mild cognitive impairment (MCI) progressing to Alzheimer disease (MCI-AD) by use of biomarkers in cerebrospinal fluid (CSF) is an essential step toward improving clinical diagnosis and drug development. We evaluated whether different β-amyloid42 (Aβ42) peptides can add further information to the combined use of tau and Aβ1–42 for predicting risk of progression of MCI to AD. Methods: We used xMAP® technology to simultaneously quantify different Aβ42 peptides modified at the amino terminus, tau, and phosphorylated tau (P-tau181P) in CSF. Aβ42 peptide concentrations were measured by use of immunoreactivity toward Aβ monoclonal antibodies [3D6 (Aβ42-3D6), WO2 (Aβ42-WO2), 6E10 (Aβ42-6E10), and 4G8 (Aβ42-4G8)]. The discriminant ability of the markers was evaluated by ROC curve analysis. Results: The areas under the curves for the separation of MCI-AD from nonprogressing MCI (MCI-N) were significantly higher when we used Aβ42-3D6/Aβ42-WO2, Aβ42-3D6/Aβ42-6E10, or Aβ42-3D6/Aβ42-4G8 compared with Aβ42-3D6. In addition, differentiation of MCI-N from MCI-AD was improved by quantification of full-length Aβ1–42 (Aβ42-3D6) compared with Aβ42-WO2, Aβ42-6E10, or Aβ42-4G8. Several Aβ42 peptides truncated at the amino terminus (Aβ11–42 and Aβ8–42) were identified in CSF by surface-enhanced laser desorption/ionization time-of-flight technology. Conclusion: The CSF markers tau, Aβ42 forms, and P-tau181P, when used as adjuncts to clinical diagnosis, have the potential to help identify AD pathology and could be a valuable asset for early AD diagnosis.

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