Dataset Information

Cerebrospinal fluid and blood A? levels in Down syndrome patients with and without dementia: a meta-analysis study.

ABSTRACT: Abnormal ?-amyloid (A?) levels were found in patients with Down syndrome (DS). However, A? levels in patients with DS and DS with dementia (DSD) vary considerably across studies. Therefore, we performed a systematic literature review and quantitatively summarized the clinical A? data on the cerebrospinal fluid (CSF) and blood of patients with DS and those with DSD using a meta-analytical technique. We performed a systematic search of the PubMed and Web of Science and identified 27 studies for inclusion in the meta-analysis. Random-effects meta-analysis indicated that the levels of blood A?_1-40 and A?_1-42 were significantly elevated in patients with DS compared with those in healthy control (HC) subjects. In contrast, there were no significant differences between patients with DS and those with DSD in the blood A?_1-40 and A?_1-42 levels. The CSF A?_1-42 levels were significantly decreased in patients with DS compared to those in HC subjects. Further, CSF A?_1-42 levels were significantly decreased in patients with DSD compared to those with DS, with a large effect size. Taken together, our results demonstrated that blood A?_1-40 and A?_1-42 levels were significantly increased in patients with DS while CSF A?_1-42, but not A?_1-40 levels were significantly decreased in patients with DS.

SUBMITTER: Du Y

PROVIDER: S-EPMC6949072 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Cerebrospinal fluid and blood Aβ levels in Down syndrome patients with and without dementia: a meta-analysis study.

Du Yang Y Chen Lei L Jiao Yuguo Y Cheng Yong Y

Aging 20191220 24

Abnormal β-amyloid (Aβ) levels were found in patients with Down syndrome (DS). However, Aβ levels in patients with DS and DS with dementia (DSD) vary considerably across studies. Therefore, we performed a systematic literature review and quantitatively summarized the clinical Aβ data on the cerebrospinal fluid (CSF) and blood of patients with DS and those with DSD using a meta-analytical technique. We performed a systematic search of the PubMed and Web of Science and identified 27 studies for in ...[more]

PMID: 31860872

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Project description:BACKGROUND:Reliable biomarkers of frontotemporal dementia (FTD) are currently lacking. FTD may be associated with chronic immune dysfunction, microglial activation and raised inflammatory markers, particularly in progranulin (GRN) mutation carriers. Levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) are elevated in Alzheimer's disease (AD), but they have not been fully explored in FTD. METHODS:We investigated whether cerebrospinal fluid (CSF) sTREM2 levels differ between FTD and controls, across different clinical and genetic subtypes of FTD, or between individuals with FTD due to AD versus non-AD pathology (based on CSF neurodegenerative biomarkers). We also assessed relationships between CSF sTREM2 and other CSF biomarkers (total tau [T-tau], tau phosphorylated at position threonine-181 [P-tau] and ?-amyloid 1-42 [A?42]) and age and disease duration. Biomarker levels were measured using immunoassays in 17 healthy controls and 64 patients with FTD (behavioural variant FTD, n?=?20; primary progressive aphasia, n?=?44). Ten of 64 had familial FTD, with mutations in GRN (n?=?3), MAPT (n?=?4), or C9orf72 (n?=?3). Fifteen of 64 had neurodegenerative biomarkers consistent with AD pathology (11 of whom had logopenic variant PPA). Levels were compared using multivariable linear regressions. RESULTS:CSF sTREM2 levels did not differ between FTD and controls or between clinical subgroups. However, GRN mutation carriers had higher levels than controls (mean ([SD]?=?9.7 [2.9] vs. 6.8 [1.6] ng/ml; P?= 0.028) and MAPT (3.9 [1.5] ng/ml; P?=?0.003] or C9orf72 [4.6 [1.8] ng/ml; P?=?0.006) mutation carriers. Individuals with AD-like CSF had higher sTREM2 levels than those with non-AD-like CSF (9.0 [3.6] vs. 6.9 [3.0] ng/ml; P?=?0.029). CSF sTREM2 levels were associated with T-tau levels in control and FTD groups and also with P-tau in those with FTD and AD-like CSF. CSF sTREM2 levels were influenced by both age and disease duration in FTD. CONCLUSIONS:Although CSF sTREM2 levels are not raised in FTD overall or in a particular clinical subtype of FTD, levels are raised in familial FTD associated with GRN mutations and in FTD syndromes due to AD pathology. Because CSF sTREM2 levels correlate with a marker of neuronal injury (T-tau), sTREM2 should be explored as a biomarker of disease intensity in future longitudinal studies of FTD.

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

Cerebrospinal fluid and blood A? levels in Down syndrome patients with and without dementia: a meta-analysis study.

Publications

Cerebrospinal fluid and blood Aβ levels in Down syndrome patients with and without dementia: a meta-analysis study.

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