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- Title
Decreased Plasma Aß in Hyperlipidemic APP<sub>SL</sub> Transgenic Mice Is Associated with BBB Dysfunction.
- Authors
Löffer, Tina; Flunkert, Stefanie; Temmel, Magdalena; Hutter-Paier, Birgit
- Abstract
Besides the continued focus on Aß and Tau in Alzheimer's disease (AD), it is increasingly evident that other pathologic characteristics, such as vascular alterations or inflammation, are associated with AD. Whether these changes are an initial cause for the onset of AD or occur as a result of the disease in late stages is still under debate. In the present study, the impact of the high-fat diet (HFD) induced vascular risk factor hyperlipidemia on Aß levels and clearance as well as cerebral vasculature and blood-brain barrier (BBB) integrity was examined in mice. For this purpose, human APP transgenic (APPSL) and wildtype (WT) mice were fed a HFD for 12 weeks. Plasma and tissues were subsequently investigated for Aß distribution and concentrations of several vascular markers. Decreased plasma Aß together with increased levels of insoluble Aß and amyloid plaques in the brains of HFD fed APPSL mice point toward impaired Aß clearance due to HFD. Additionally, HFD induced manifold alterations in the cerebral vasculature and BBB integrity exclusively in human APP overexpressing mice but not in wildtype mice. Therefore, HFD appears to enhance Aß dependent vascular/BBB dysfunction in combination with an increased proportion of cerebral to plasma Aß in APPSL mice.
- Subjects
ALZHEIMER'S disease; HIGH-fat diet; CEREBROVASCULAR disease; NUTRITION
- Publication
Frontiers in Neuroscience, 2016, p1
- ISSN
1662-4548
- Publication type
Article
- DOI
10.3389/fnins.2016.00232