Dataset Information

Longitudinal analysis of novel Alzheimer's disease proteomic cerebrospinal fluid biomarkers during intravenous immunoglobulin therapy.

ABSTRACT: Intravenous immunoglobulin (IVIg) therapy has shown promising results in treating Alzheimer's disease (AD). In this study, a Random Forest (RF) classification model was used to identify possible effects of IVIg on a group of eight subjects who underwent immunotherapy. Cerebrospinal fluid (CSF) samples from eight AD subjects who underwent IVIg therapy were collected before therapy, after 6 months of therapy, and after a 3-month drug washout period. Samples were analyzed using 2DE and further studied using a RF classification model to identify effects of IVIg on a panel of 23 putative diagnostic AD biomarkers previously identified. Six of the eight subjects showed improvements with respect to the 23 AD diagnostic biomarkers after 6 months of therapy compared to the samples taken at the outset of the trial. All subjects reverted back to baseline during drug washout. These results are also consistent with clinical observations. The observed improvements in subjects during 6 months of IVIg therapy and the reversion back to baseline during drug washout provides preliminary evidence regarding the potential use of IVIg as an AD immunotherapy.

SUBMITTER: Shayan G

PROVIDER: S-EPMC5827947 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Longitudinal analysis of novel Alzheimer's disease proteomic cerebrospinal fluid biomarkers during intravenous immunoglobulin therapy.

Shayan Gilda G Adamiak Basia B Relkin Norman R NR Lee Kelvin H KH

Electrophoresis 20120701 13

Intravenous immunoglobulin (IVIg) therapy has shown promising results in treating Alzheimer's disease (AD). In this study, a Random Forest (RF) classification model was used to identify possible effects of IVIg on a group of eight subjects who underwent immunotherapy. Cerebrospinal fluid (CSF) samples from eight AD subjects who underwent IVIg therapy were collected before therapy, after 6 months of therapy, and after a 3-month drug washout period. Samples were analyzed using 2DE and further stud ...[more]

PMID: 22806462

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Project description:Widespread implementation of cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) in clinical settings requires improved accuracy for diagnosis of prodromal disease and for distinguishing AD from non-AD dementias. Novel and promising CSF biomarkers include neurogranin, a marker of synaptic degeneration, and YKL-40, a marker of neuroinflammation.CSF neurogranin and YKL-40 were measured in a cohort of 338 individuals including cognitively healthy controls and patients with stable mild cognitive impairment (sMCI), MCI who later developed AD (MCI-AD), AD dementia, Parkinson's disease dementia (PDD), dementia with Lewy bodies (DLB), vascular dementia (VaD), and frontotemporal dementia (FTD). The diagnostic accuracy of neurogranin and YKL-40 were compared with the core AD biomarkers, β-amyloid (Aβ42 and Aβ40) and tau.Neurogranin levels were increased in AD and decreased in non-AD dementia compared with healthy controls. As a result, AD patients showed considerably higher CSF levels of neurogranin than DLB/PDD, VaD and FTD patients. CSF YKL-40 levels were increased in AD compared with DLB/PDD but not with VaD or FTD. Neither CSF neurogranin nor YKL-40 levels differed significantly between sMCI patients and MCI-AD patients. Both biomarkers correlated positively with CSF Aβ40 and tau. CSF neurogranin and YKL-40 could separate AD dementia from non-AD dementias (neurogranin, area under the curve [AUC] = 0.761; YKL-40, AUC = 0.604; Aβ42/neurogranin, AUC = 0.849; Aβ42/YKL-40, AUC = 0.785), but the diagnostic accuracy was not better compared to CSF Aβ and tau (Aβ42, AUC = 0.755; tau AUC = 0.858; Aβ42/tau, AUC = 0.895; Aβ42/Aβ40, AUC = 0.881). Similar results were obtained when separating sMCI from MCI-AD cases.CSF neurogranin and YKL-40 do not improve the diagnostic accuracy of either prodromal AD or AD dementia when compared to the core CSF AD biomarkers. Nevertheless, the CSF level of neurogranin is selectively increased in AD dementia, whereas YKL-40 is increased in both AD and FTD suggesting that synaptic degeneration and glial activation may be important in these neurodegenerative conditions.

Dataset Information

Longitudinal analysis of novel Alzheimer's disease proteomic cerebrospinal fluid biomarkers during intravenous immunoglobulin therapy.

Publications

Longitudinal analysis of novel Alzheimer's disease proteomic cerebrospinal fluid biomarkers during intravenous immunoglobulin therapy.

Similar Datasets

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