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P1‐337: African American Brain Autopsies from The National Alzheimer’s Coordinating Center
Author(s) -
Graff-Radford Neill R.,
Besser Lilah M.,
Crook Julia E.,
Kukull Walter A.,
Dickson Dennis W.
Publication year - 2016
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.2016.06.1088
Subject(s) - pathological , dementia , pathology , apolipoprotein e , senile plaques , medicine , neuropathology , vascular dementia , cerebral amyloid angiopathy , disease , alzheimer's disease , lewy body
bles, transiently induces blood-brain barrier (BBB) permeability to allow for minimally invasive delivery of therapeutics, to targeted areas of the brain. Restoration of the BBB following FUS occurs rapidly in healthy models, however, the primary clinical use would be in neurological disorders, such as Alzheimer’s disease (AD), where BBB integrity may be compromised. The use of FUS to deliver AD therapeutics could have beneficial clinical implications, however, it is unknown whether the plasticity of the BBB and its capacity for repair is maintained in the presence of AD pathology. Furthermore, we sought to accelerate BBB restoration using Vasculotide (VT), a synthetic angiopoietin-1 mimetic that activates the Tie2 signaling cascade; a pathway known to promote vascular stability and cell survival in peripheral organs.Methods:Using a transgenic (Tg) mouse model of amyloidosis and their non-Tg littermates, VT was injected, every 48 hours for 2-3 months. We used FUS to induce transient increases in BBB permeability. The entry of gadolinium in the brain was monitored by MRI and quantified using MATLAB at 6, 12 and 20 hours post-FUS. Lastly, in a separate cohort of mice, Evans Blue dye was injected to evaluate BBB closure 24 hours post-FUS. Results: VT significantly accelerated BBB restoration, with no significant difference between Tg and non-Tg mice. Furthermore, VT reduced the initial enhancement and acoustic pressure required to induce BBB permeability, with no difference between Tg and non-Tg mice. Finally, Evans Blue dye injected 24 hours post-FUS confirmed BBB closure. Conclusions:Our research is the first to examine the effects of VT on BBB permeability and provides a better understanding of the effects of FUS. This research presents a novel method of facilitating BBB closure that could lead to a VT pre-treatment with FUS delivery of AD therapeutics.