Dataset Information

Increased CSF Aβ during the very early phase of cerebral Aβ deposition in mouse models.

ABSTRACT: Abnormalities in brains of Alzheimer's disease (AD) patients are thought to start long before the first clinical symptoms emerge. The identification of affected individuals at this 'preclinical AD' stage relies on biomarkers such as decreased levels of the amyloid-β peptide (Aβ) in the cerebrospinal fluid (CSF) and positive amyloid positron emission tomography scans. However, there is little information on the longitudinal dynamics of CSF biomarkers, especially in the earliest disease stages when therapeutic interventions are likely most effective. To this end, we have studied CSF Aβ changes in three Aβ precursor protein transgenic mouse models, focusing our analysis on the initial Aβ deposition, which differs significantly among the models studied. Remarkably, while we confirmed the CSF Aβ decrease during the extended course of brain Aβ deposition, a 20-30% increase in CSF Aβ40 and Aβ42 was found around the time of the first Aβ plaque appearance in all models. The biphasic nature of this observed biomarker changes stresses the need for longitudinal biomarker studies in the clinical setting and the search for new 'preclinical AD' biomarkers at even earlier disease stages, by using both mice and human samples. Ultimately, our findings may open new perspectives in identifying subjects at risk for AD significantly earlier, and in improving the stratification of patients for preventive treatment strategies.

SUBMITTER: Maia LF

PROVIDER: S-EPMC4520655 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Increased CSF Aβ during the very early phase of cerebral Aβ deposition in mouse models.

Maia Luis F LF Kaeser Stephan A SA Reichwald Julia J Lambert Marius M Obermüller Ulrike U Schelle Juliane J Odenthal Jörg J Martus Peter P Staufenbiel Matthias M Jucker Mathias M

EMBO molecular medicine 20150701 7

Abnormalities in brains of Alzheimer's disease (AD) patients are thought to start long before the first clinical symptoms emerge. The identification of affected individuals at this 'preclinical AD' stage relies on biomarkers such as decreased levels of the amyloid-β peptide (Aβ) in the cerebrospinal fluid (CSF) and positive amyloid positron emission tomography scans. However, there is little information on the longitudinal dynamics of CSF biomarkers, especially in the earliest disease stages whe ...[more]

PMID: 25978969

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Project description:ObjectiveTo investigate the correlation between the swelling rate of brain volume within the first 48 h after aneurysmal subarachnoid hemorrhage and the subsequent development of delayed cerebral ischemia.MethodsA retrospective analysis was conducted on patients with spontaneous aneurysmal subarachnoid hemorrhage admitted to the Neurosurgery Intensive Care Unit of the First Affiliated Hospital of Chongqing Medical University between January 2020 and January 2023. The clinical data, treatment outcomes, and imaging data were analyzed. Brain volume was evaluated using 3D-Slicer software at two time points post-hemorrhage: within the first 24 h and between 24 and 48 h. The swelling rate of brain volume was defined as the ratio of the absolute difference between two measurements to the smaller of values. Patients were categorized into two groups based on established diagnostic criteria of delayed cerebral ischemia. Univariate and multivariate logistic regression analyses were performed to identify factors influencing delayed cerebral ischemia.ResultsA total of 140 patients were enrolled in this study. 46 patients experienced delayed cerebral ischemia after bleeding. The swelling rate of brain volume was larger in the DCI group (10.66 ± 8.45) compared to the non-DCI group (3.59 ± 2.62), which showed a statistically significant difference. Additionally, advanced age, smoking history, history of hypertension, loss of consciousness, poor Hunt-Hess grade, high mFisher score, brain volume within 24 h, and IVH were also statistically different between the two groups. Multivariate logistic regression analysis revealed that the swelling rate of brain volume was an independent risk factor for DCI with adjusting the advanced age, smoking history, history of hypertension, poor Hunt-Hess grade, high mFisher score, brain volume within 24 h, and IVH.ConclusionBrain volume significantly increased in patients with aneurysmal subarachnoid hemorrhage during the early phase (within 48 h post-onset). The larger swelling rate of brain volume is an independent risk factor for the development of delayed cerebral ischemia, and it may hold significant predictive value for the incidence of delayed cerebral ischemia.

Dataset Information

Increased CSF Aβ during the very early phase of cerebral Aβ deposition in mouse models.

Publications

Increased CSF Aβ during the very early phase of cerebral Aβ deposition in mouse models.

Similar Datasets

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