| First Author | Maia LF | Year | 2015 |
| Journal | EMBO Mol Med | Volume | 7 |
| Issue | 7 | Pages | 895-903 |
| PubMed ID | 25978969 | Mgi Jnum | J:233464 |
| Mgi Id | MGI:5784804 | Doi | 10.15252/emmm.201505026 |
| Citation | Maia LF, et al. (2015) Increased CSF Abeta during the very early phase of cerebral Abeta deposition in mouse models. EMBO Mol Med 7(7):895-903 |
| abstractText | 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-beta peptide (Abeta) 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 Abeta changes in three Abeta precursor protein transgenic mouse models, focusing our analysis on the initial Abeta deposition, which differs significantly among the models studied. Remarkably, while we confirmed the CSF Abeta decrease during the extended course of brain Abeta deposition, a 20-30% increase in CSF Abeta40 and Abeta42 was found around the time of the first Abeta 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. |
