Open AccessIncreased CSF Aβ during the very early phase of cerebral Aβ deposition in mouse models
Author(s) -
Maia Luis F,
Kaeser Stephan A,
Reichwald Julia,
Lambert Marius,
Obermüller Ulrike,
Schelle Juliane,
Odenthal Jörg,
Martus Peter,
Staufenbiel Matthias,
Jucker Mathias
Publication year - 2015
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201505026
Subject(s) - deposition (geology) , phase (matter) , chemistry , microbiology and biotechnology , cerebrospinal fluid , biophysics , biology , neuroscience , paleontology , organic chemistry , sediment
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.