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Increase in CSF Abeta during the very early phase of cerebral Abeta deposition in mouse models

Maia, Luis F and Kaeser, Stephan A and Reichwald, Julia and Lambert, Marius and Obermüller, Ulrike and Odenthal, Jörg and Martus, Peter and Staufenbiel, Matthias and Jucker, Mathias (2015) Increase in CSF Abeta during the very early phase of cerebral Abeta deposition in mouse models. EMBO Mol Med.

Abstract

Abnormalities in the brain 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 β-amyloid peptide (Aβ) in the cerebrospinal fluid (CSF) and brain retention of amyloid-binding agents using positron emission tomography. However, these biomarkers are limited by the lack of longitudinal profiles and lack pathological conformation in brain.
To this end we have studied CSF Aβ changes in three genetically-defined amyloid precursor protein (APP) transgenic mouse models focusing our analysis on the time of the initial Aβ deposition in brain, which differs significantly between the models studied. Remarkably, while we confirmed the CSF Aβ decrease during the course of brain amyloid deposition, a temporary 20-30% increase in CSF Aβ40 and 42 was found at the time of the appearance of the first individual Aβ plaques in all the three models.
These results together with emerging indications of similar CSF Aβ increases at very early stages in familial and sporadic AD suggest that increased CSF Aβ levels may constitute the first detectable biomarker change in the AD pathological process. This important observation opens new perspectives in patient selection and stratification for preventive treatment strategies and is an incentive to the discovery of additional “preclinical AD” biomarkers.

Item Type: Article
Keywords: Alzheimer's Disease, APP transgenic Mice, amyloid-beta, biomarker
Date Deposited: 04 May 2016 23:45
Last Modified: 04 May 2016 23:45
URI: https://oak.novartis.com/id/eprint/22558

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