Premium
P1‐096: PRECLINICAL STUDIES OF NOROVIRUS P PARTICLE‐BASED ACTIVE Aβ IMMUNOTHERAPIES FOR ALZHEIMER'S DISEASE
Author(s) -
Fu Lu,
Li Yingnan,
Wu Hui,
Yu Xianghui,
Kong Wei
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.098
Subject(s) - immunogenicity , medicine , disease , vaccination , immunology , immunotherapy , clinical trial , epitope , dementia , immune system , antibody
Background: Focused Ultrasound (FUS)-induced blood-brain barrier opening has been shown to eliminate 52% of the amyloid plaque load and reduce the misfolded tau protein from both the entorhinal cortex and the axonal compartment of the hippocampus. Since the effect of ultrasound has been proven beneficial when studying the AD pathologies separately, it is essential to investigate, for the first time, the interaction of FUS-induced BBB opening in the presence of both amyloid-b and tau. Moreover, the unilateral sonication of the transgenic brain provides a unique opportunity to explore potential bilateral effects. Methods: For this study 9 mice of the 3xTg line (11 months old) were randomly assigned to the control and treatment group with the later receiving a double sonication covering the hippocampal region once per week for 4 consecutive weeks. Following the last sonication the mice were sacrificed and counterstained for tau protein (AT8), amyloid-b (Ab42-specific antibody) as well as microglia activation (CD68). The images were acquired by means of confocal microscopy and customized algorithms were constructed to quantify the number of plaques, cells and the axonal distribution of the tau-marker. The same brain slices were utilized to quantify the hippocampal density of the CD68 marker by intensity-based quantification. Results: In Figure 1, the phosphorylated tau is shown to be present in both the somatodendritic and the axonal compartment (red) in the contralateral side. Although the cell bodies affected by