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Addition of the A?42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment.

ABSTRACT: BACKGROUND:Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF A?42 concentration to the level of total amyloid beta (A?), using the A?42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the A?42/40 ratio would improve MCI categorization and more accurately predict progression to AD. METHODS:Our baseline population consisted of 197 MCI patients, of which 144 had a follow-up ??2 years, and comprised the longitudinal study group. To establish our own CSF A?42/40 ratio reference value, a group of 168 AD-dementia patients and 66 neurological controls was also included. CSF biomarker-based classification was operationalized according to the framework of the National Institute of Aging-Alzheimer Association criteria for MCI. RESULTS:When using the core CSF biomarkers (A?42, total Tau and phosphorylated Tau), 30% of the patients fell into the high-AD-likelihood (HL) group (both amyloid and neurodegeneration markers positive), 30% into the low-AD-likelihood group (all biomarkers negative), 28% into the suspected non-Alzheimer pathophysiology (SNAP) group (only neurodegeneration markers positive) and 12% into the isolated amyloid pathology group (only amyloid-positive). Replacing A?42 by the A?42/40 ratio resulted in a significant increase in the percentage of patients with amyloidosis (42-59%) and in the proportion of interpretable biological profiles (61-75%), due to a reduction by half in the number of SNAP cases and an increase in the proportion of the HL subgroup. Survival analysis showed that risk of progression to AD was highest in the HL group, and increased when the A?42/40 ratio, instead of A?42, combined with total Tau and phosphorylated Tau was used for biomarker-based categorization. CONCLUSIONS:Our results confirm the usefulness of the CSF A?42/40 ratio in the interpretation of CSF biomarker profiles in MCI patients, by increasing the proportion of conclusive profiles and enhancing their predictive value for underlying AD.

SUBMITTER: Baldeiras I

PROVIDER: S-EPMC5861634 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Addition of the Aβ42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment.

Baldeiras Inês I Santana Isabel I Leitão Maria João MJ Gens Helena H Pascoal Rui R Tábuas-Pereira Miguel M Beato-Coelho José J Duro Diana D Almeida Maria Rosário MR Oliveira Catarina Resende CR

Alzheimer's research & therapy 20180320 1

<h4>Background</h4>Cerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer's disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aβ42 concentration to the level of total amyloid beta (Aβ), using the Aβ42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we ev ...[more]

PMID: 29558986

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Project description:ObjectiveThe prognostic value of cerebrospinal fluid neurofilament light chain, total tau, phosphorylated tau181, and amyloid beta1-42 was examined in frontotemporal dementia subtypes.MethodsWe compared baseline biomarkers between 49 controls, 40 patients with behavioral variant frontotemporal dementia, 24 with semantic variant primary progressive aphasia, and 26 with nonfluent variant primary progressive aphasia. Linear mixed effect models were used to assess the value of baseline biomarkers in predicting clinical and radiographic change in patient cohorts over multiple yearly follow up visits.ResultsNeurofilament light chain concentrations were lowest in controls. Elevated baseline neurofilament light chain predicted faster worsening in clinical severity, frontotemporal volume and frontotemporal fractional anisotropy in patients with behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. High total tau similarly predicted faster progression in nonfluent variant primary progressive aphasia. In behavioral variant frontotemporal dementia, higher phosphorylated tau181 predicted faster clinical progression whereas lower amyloid beta1-42 predicted faster volumetric and fractional anisotropy reduction. Neurofilament light chain and phosphorylated tau181 were of greater predictive value in patients with tau pathology as compared to TDP-43 pathology. Baseline neurofilament light chain correlated with baseline clinical severity and frontotemporal volume in behavioral variant frontotemporal dementia. Baseline total tau correlated with baseline clinical severity in semantic variant primary progressive aphasia.InterpretationHigh cerebrospinal fluid neurofilament light chain predicts more aggressive disease in behavioral variant frontotemporal dementia and nonfluent variant primary progressive aphasia. Total tau, phosphorylated tau181, and amyloid beta1-42 also predict some measures of disease aggressiveness in frontotemporal dementia.

Dataset Information

Addition of the A?42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment.

Publications

Addition of the Aβ42/40 ratio to the cerebrospinal fluid biomarker profile increases the predictive value for underlying Alzheimer's disease dementia in mild cognitive impairment.

Similar Datasets

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