Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease

Quiroz, Yakeel T.; Schultz, Aaron P.; Chen, Kewei; Protas, Hillary; Brickhouse, Michael; Fleisher, Adam; Langbaum, Jessica B.; Thiyyagura, Pradeep; Fagan, Anne M.; Shah, Aarti R.; Muniz, Martha; Arboleda‐Velásquez, Joseph F.; Muñoz, Claudia; García, Gloria; Acosta‐Baena, Natalia; Giraldo, Margarita; Tirado, Victoria; Ramirez, Dora; Tariot, Pierre N.; Dickerson, Bradford C.; Sperling, Reisa A.; Lopera, Francisco; Reiman, Eric M.

doi:10.1001/jamaneurol.2015.1099

Cited by 102 publications

(115 citation statements)

References 33 publications

(38 reference statements)

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“…35 There is an association between decreased CSF Ab42 and autosomal dominant AD. 36 In previous studies, CSF Ab42 increased after msTBI, with a peak on Day 6 after the injury, 37 but without a detectable increase in peripheral blood.…”

Section: Discussionmentioning

confidence: 81%

Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Bogoslovsky

Wilson

Yao

et al. 2017

Journal of Neurotrauma

172

126

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Glial fibrillary acidic protein (GFAP), microtubule-associated protein tau, and amyloid b peptide (Ab42) have been proposed as diagnostic and prognostic biomarkers in traumatic brain injury (TBI). Single molecule array (Simoa) is a novel technology that employs highly sensitive immunoassays for accurate measurements of candidate biomarkers found at low concentration in biological fluids. Our objective was to trace the trajectory of tau, GFAP, and Ab42 levels in plasma from the acute through subacute stages after TBI, compared with controls. Samples from 34 TBI subjects enrolled in the Citicoline Brain Injury Treatment Trial (COBRIT) were studied. Injury severity was assessed by Glasgow Coma Scale (GCS) and admission CT. Glasgow Outcome Scale Extended (GOSE) was assessed 6 months after injury. Plasma was collected within 24 h (Day 0), and 30 and 90 days after the TBI. Plasma collected from 69 healthy volunteers was used for comparison. At every time point, increases were noted in plasma GFAP ( p < 0.0001 for all comparisons), tau ( p < 0.0001, p < 0.0001, and p = 0.0044, at Days 0, 30, and 90, respectively), and Ab42 ( p < 0.001, p < 0.0001, and p = 0.0203, respectively) in TBI cases compared with controls. The levels were maximal at Day 0 for GFAP and tau and at Day 30 for Ab42. Area under curve (AUC) analyses for Day 0 GFAP and tau were excellent for discrimination of complicated mild TBI (cmTBI) from controls (0.936 and 0.901, correspondingly). Discriminant component analysis (DCA) for all three biomarkers at Days 0 and 30 differentiated controls from cmTBI (91.1% and 89.7% correctly classified, at each time point). Duration of post-traumatic amnesia (PTA) correlated weakly with tau levels at 30 days (Spearman's r = 0.40; 95% CI 0.0003-0.60, p = 0.044). The Marshall CT Grade on admission correlated weakly with Day 30 tau levels (Spearman's r = 0.41; 95% CI 0.04-0.68, p = 0.027). Day 30 Ab42 correlated with GOSE (standardized b -0.486, p = 0.042). GFAP, tau and Ab42 were increased up to 90 days after TBI compared with controls. Total tau levels correlated with clinical and radiological variables of TBI severity. Plasma Ab42 correlated with clinical outcome. Combination of all three biomarkers at Days 0 and 30 can be used to differentiate controls from cmTBI populations, and may be useful as biomarkers of TBI in both acute and subacute phases.

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Section: Discussionmentioning

confidence: 81%

Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Bogoslovsky

Wilson

Yao

et al. 2017

Journal of Neurotrauma

172

126

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“…These differences have also been identified in regional brain activity using positron emission tomography [10], functional magnetic resonance imaging [11,12] and proton magnetic resonance spectroscopy [13]. A recent study, in children in the age range of 9 to 17 years old, has identified functional and structural brain changes and abnormal levels of plasma amyloid-β-1-42, constituting the earliest biomarkers associated with E280A mutation [14].…”

Section: Introductionmentioning

confidence: 99%

Precuneus Failures in Subjects of the PSEN1 E280A Family at Risk of Developing Alzheimer’s Disease Detected Using Quantitative Electroencephalography

Villa-Ochoa

Alonso

Duque

et al. 2017

JAD

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Background: Presenilin-1 (PSEN1) mutations are the most common cause of familial early onset Alzheimer's Disease (AD). The PSEN1 E280A (E280A) mutation has an autosomal dominant inheritance and is involved in the production of amyloid-β. In Antioquia, Colombia, there is the largest family group of carriers with E280A mutation. The study of mutation carriers provides an unique opportunity to identify brain changes in stages previous to AD. Electroencephalography (EEG) is a low cost and minimally invasiveness technique that enables the following of brain changes in AD.Objective: To examine how previous reported differences in EEG for Theta and Alpha-2 rhythms in E280A subjects are related to specific regions in cortex and could be tracked across different ages. Methods: EEG signals were acquired during resting state from non-carriers and carriers, asymptomatic and symptomatic, subjects from E280A kindred from Antioquia, Colombia. Independent Component Analysis and inverse solution methods were used to locate brain regions related to differences in Theta and Alpha-2 bands.Results: Independent Component Analysis helps to identify two components, mainly related to the Precuneus, were the differences in Theta and Alpha-2 exist simultaneously at asymptomatic and symptomatic stage. When a ratio between Theta and Alpha-2 is used significant correlations exist with age and a composite cognitive scale. Conclusion:Theta and Alpha-2 rhythms are altered in E280A subjects. The alterations are possible to track at Precuneus regions using EEG, ICA and inverse solution methods.

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“…Recent studies of plasma Aβ levels have shown that they recapitulate the same sink-model trends observed in CSF (albeit with considerably lower Aβ levels in plasma): higher than normal Aβ1-42 levels at preclinical stages, which drop longitudinally with disease onset and progression. This paradigm is supported by the following observations: (i) higher levels in early onset, genetically associated AD, such as in Down's syndrome and autosomal dominant AD (ADAD), and even as early as children with ADAD [11]; (ii) higher levels in animal models prior to disease onset [17]; (iii) associations with cognitive change in normal individuals [14]; and (iv) association between plasma and CSF levels [18], in longitudinal studies being predictive of progression to AD [19]. For plasma Aβ, some empirical questions that still need to be resolved are as follows: (i) How much is derived from the CNS versus peripheral sources?…”

mentioning

confidence: 90%

“…These measures include positron emission tomography assay of amyloid deposition in the brain, as well as soluble forms such as cerebrospinal fluid (CSF) Aβ1-40, Aβ1-42 monomers, the Aβ1-42/Aβ1-40 ratio, and/or oligomers of Aβ. A growing body of evidence shows that changes to these various Aβ forms occur at preclinical stages of late onset AD [10]; the soluble multimers/oligomers are the most toxic forms [5]; they are early features of familial AD [11]; their accumulation/aggregation temporally precedes tau dysregulation [4]; and, tau is neurotoxic but in the absence of Aβ aggregation does not lead to AD [3]. Therefore, Aβ measurement will no doubt continue to be of interest as both a research and a clinical tool.…”

mentioning

confidence: 99%

Plasma amyloid beta peptides: an Alzheimer’s conundrum or a more accessible Alzheimer’s biomarker?

Poljak

Sachdev

2016

Expert Review of Neurotherapeutics

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Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease

Cited by 102 publications

References 33 publications

Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Increases of Plasma Levels of Glial Fibrillary Acidic Protein, Tau, and Amyloid β up to 90 Days after Traumatic Brain Injury

Precuneus Failures in Subjects of the PSEN1 E280A Family at Risk of Developing Alzheimer’s Disease Detected Using Quantitative Electroencephalography

Plasma amyloid beta peptides: an Alzheimer’s conundrum or a more accessible Alzheimer’s biomarker?

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