Evaluation of Cerebrospinal Fluid Tau/Beta-Amyloid(42) Ratio as Diagnostic Markers for Alzheimer Disease

Smach, Mohamed Ali; Charfeddine, Bassem; Othman, Leila Ben; Lammouchi, Turkia; Dridi, Hedi; Nafati, Souhir; Ltaief, Afef; Bennamou, Soufien; Limem, Khalifa

doi:10.1159/000241881

Cited by 27 publications

(13 citation statements)

References 58 publications

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“… 6 Given this variability, it would be very useful to have reliable markers which can predict AD dementia progression among amnestic MCI individuals. 7 There are many evidences supporting that various neuropsychological, 8 9 10 11 12 13 14 neuroimaging, 15 16 17 18 19 genetic 20 21 22 and biochemical markers 23 24 25 26 or their combinations 3 27 could predict the progression to AD dementia in MCI individuals. However, many of these markers have some limitations to be used in real clinical settings because they are complicated, expensive, invasive, or sometime unavailable.…”

Section: Introductionmentioning

confidence: 99%

Clinical Dementia Rating Orientation Score as an Excellent Predictor of the Progression to Alzheimer's Disease in Mild Cognitive Impairment

Kim

Byun

Sohn

et al. 2017

Psychiatry Investig

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ObjectiveThis study aimed to examine the usefulness of each subscale score of the Clinical Dementia Rating (CDR) for predicting Alzheimer's disease (AD) dementia progression in amnestic mild cognitive impairment (MCI) elderly subjects.MethodsFifty-nine elderly MCI individuals were recruited from a university dementia and memory disorder clinic. Standardized clinical and neuropsychological tests were performed both at baseline and at the time of 2 years follow-up. Logistic regression analyses were conducted to examine the ability of various clinical measures or their combinations to predict progression to AD dementia in MCI individuals.ResultsMCIp individuals showed significantly higher CDR Orientation subscale and CDR sum-of-boxes (SOB) score than MCInp ones, while there were no significant differences in other CDR subscale scores between the two. MCIp individuals also showed marginally higher MMSE scores than MCInp ones. A series of logistic regression analyses demonstrated that the model including CDR Orientation subscale had better AD dementia prediction accuracy than either the model with either MMSE or CDR-SOB.ConclusionOur findings suggest that CDR Orientation subscale score, a simple and easily available clinical measure, could provide very useful information to predict AD dementia progression in amnestic MCI individuals in real clinical settings.

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Section: Introductionmentioning

confidence: 99%

Clinical Dementia Rating Orientation Score as an Excellent Predictor of the Progression to Alzheimer's Disease in Mild Cognitive Impairment

Kim

Byun

Sohn

et al. 2017

Psychiatry Investig

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“…Several cerebrospinal fluid (CSF) markers that are presumably related to the core pathology in AD show promise for early detection of the disease. Lower levels of CSF Aβ 42 , higher CSF total tau (T-Tau), and higher tau phosphorylated at threonine 181 (P-Tau 181 ), as well as biomarker ratios (T-Tau/Aβ 42 or P-Tau/Aβ 42 ) distinguish patients from controls [1], [2], [3], [4], [5] and predict conversion from mild cognitive impairment (MCI) to AD [1], [2], [6], [7], [8], [9]. When evaluated in cognitively healthy individuals, these biomarkers also appear to be related to cognitive function [10], [11], and measures of brain health that include cortical thinning [12], ventricular expansion and atrophy [11], [13], [14], [15], [16].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, because T1-weighted imaging may inform upon atrophy, we assessed the extent to which biomarkers in CSF were related to volume as assessed via T1-weighted imaging. Based on their utility in distinguishing AD patients from controls [1], [2], [3], [4], [5], the CSF biomarkers considered in this study were T-Tau, P-Tau 181 , and Aβ 42 . In addition to these markers of AD pathology, we analyzed CSF for a structural protein of neurons that is predominantly localized in large-caliber axons (and thus likely sensitive to axonal degeneration in white matter): neurofilament light chain protein (NFL) [54].…”

Section: Introductionmentioning

confidence: 99%

CSF T-Tau/Aβ42 Predicts White Matter Microstructure in Healthy Adults at Risk for Alzheimer’s Disease

et al. 2012

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Cerebrospinal fluid (CSF) biomarkers T-Tau and Aβ42 are linked with Alzheimer’s disease (AD), yet little is known about the relationship between CSF biomarkers and structural brain alteration in healthy adults. In this study we examined the extent to which AD biomarkers measured in CSF predict brain microstructure indexed by diffusion tensor imaging (DTI) and volume indexed by T1-weighted imaging. Forty-three middle-aged adults with parental family history of AD received baseline lumbar puncture and MRI approximately 3.5 years later. Voxel-wise image analysis methods were used to test whether baseline CSF Aβ42, total tau (T-Tau), phosphorylated tau (P-Tau) and neurofilament light protein predicted brain microstructure as indexed by DTI and gray matter volume indexed by T1-weighted imaging. T-Tau and T-Tau/Aβ42 were widely correlated with indices of brain microstructure (mean, axial, and radial diffusivity), notably in white matter regions adjacent to gray matter structures affected in the earliest stages of AD. None of the CSF biomarkers were related to gray matter volume. Elevated P-Tau and P-Tau/Aβ42 levels were associated with lower recognition performance on the Rey Auditory Verbal Learning Test. Overall, the results suggest that CSF biomarkers are related to brain microstructure in healthy adults with elevated risk of developing AD. Furthermore, the results clearly suggest that early pathological changes in AD can be detected with DTI and occur not only in cortex, but also in white matter.

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“…However, there was a significant increase in phospho-tau levels in the NPH patient group with illness for over a year vs. NNC. Furthermore, it was previously observed that older individual with an increased ratio of tau proteins to Aβ (1–42) levels in CSF would develop early cognitive impairment compared to those individuals with decreased ratio of tau proteins to Aβ (1–42) level in CSF(Faganet al, 2007; Smach et al, 2009). We have observed an increased ratio (~3:1) of phospho-tau to Aβ (1–42) level in the CSF of NPH patients vs. NNC indicating a possible conversion to cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

Biochemical studies in Normal Pressure Hydrocephalus (NPH) patients: Change in CSF levels of amyloid precursor protein (APP), amyloid-beta (Aβ) peptide and phospho-tau

Ray

Reyes

Lahiri

2011

Journal of Psychiatric Research

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Normal Pressure Hydrocephalus (NPH) is one of the causes of dementia of the elderly characterized by impaired mental function, gait difficulties and urinary incontinence. Previously, it was proposed that some of the NPH patients may develop Alzheimer’s disease (AD) like pathology. Aim of this study was to compare levels of different CSF biomarkers, including total secreted β-amyloid precursor protein (sAPP), sAPP-alpha form (sAPPα), amyloid-beta (Aβ) peptide, total-tau protein and hyperphosphorylated-tau protein in subjects from NPH and Non-NPH Control (NNC). CSF was collected from 23 NPH patients and 13 Non-NPH controls by lumber puncture. Western blot analysis was performed to measure levels of sAPP-total. ELISA was used separately to determine levels of sAPPα, Aβ peptide, total-tau and phosphor-tau proteins. We found a significant decrease in levels of total secreted APP, sAPPα and Aβ (1–42) in the CSF sample of NPH patients vs. NNC. We did not observe any change in levels of total-tau or phospho-tau in NPH vs. NNC subjects. Notably, phospho-tau level was significantly increased in the NPH patients, who were suffering from the disease for more than one year, vs. NNC. Among five biomarkers studied, decreased sAPP, sAPPα and Aβ (1–42) levels in CSF can be molecular markers to distinguish NPH cases from NNC. Disease severity can also be assessed by increased levels of CSF phospho-tau protein and the ratio of phospho-tau to Aβ (1–42), which might be a useful tool for predicting conversion of NPH individuals to other neurodegenerative disorders including Alzheimer’s disease (AD).

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Evaluation of Cerebrospinal Fluid Tau/Beta-Amyloid(42) Ratio as Diagnostic Markers for Alzheimer Disease

Cited by 27 publications

References 58 publications

Clinical Dementia Rating Orientation Score as an Excellent Predictor of the Progression to Alzheimer's Disease in Mild Cognitive Impairment

Clinical Dementia Rating Orientation Score as an Excellent Predictor of the Progression to Alzheimer's Disease in Mild Cognitive Impairment

CSF T-Tau/Aβ42 Predicts White Matter Microstructure in Healthy Adults at Risk for Alzheimer’s Disease

Biochemical studies in Normal Pressure Hydrocephalus (NPH) patients: Change in CSF levels of amyloid precursor protein (APP), amyloid-beta (Aβ) peptide and phospho-tau

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