Abstract Details

Title Targeting of Peripheral Innate Immunity by Nasal Proteosome-Based Vaccine To Treat Alzheimer's Disease

Topic Aging and Dementia

Presentation(s) P01 - (-)

Poster/Presentation
Number 019

Objective

Background We previously found that nasal treatment of AD-Tg mice with a proteosome-based molecule (Protollin) reduced A? burden co-localized with activated CD11b+ cells. In the current study we evaluated the effect of nasal treatment with proteosome-based new compound (V2) on immunomodulation and recruitment of peripheral monocytes distinguished from brain microglia using our novel tools.

Design/Methods WT young (2-months old) or APP/PS1-Tg and WT littermates (18-months old) were treated nasally with V2 compound (OMP from Neisseria meningitides 8047) every 2nd day for 2 and 3 weeks, respectively. FACS and immunohistochemical analysis were used to evaluate cell recruitment and A? levels. Brain microglia, recruited and splenic monocytes were distinguished and isolated using our novel unique antibodies and profiled by Nanostring to determine immune-related gene signature.

Results V2 treatment induced A? uptake in mouse microglia and macrophage cell lines and human blood monocytes in vitro. In V2-treated young WT mice, Ly6CHi splenic monocytes had prominent expression of both pro-inflammatory genes (e.g. TLR's, Myd88, Stat1, IL-1?) and anti-inflammatory genes (e.g. TGF?1) with cell movement and leukocytes differentiation pathways being most significantly upregulated. We found minimal changes in gene expression of brain microglia and splenic Ly6CLow monocytes. In contrast to young mice, V2 treatment in old AD-Tg mice activated splenic Ly6Clow and brain resident microglia and reduced A?-plaques size in female mice.

Conclusions Nasal V2 treatment affects 1) induces A?-uptake in human monocytes in-vitro; 2) inflammatory signature and induces recruitment of peripheral monocyte to the brain of AD-Tg mice; 3) differentially affects monocytes and microglia in an aged-dependent manner. Thus, targeting of innate immunity by nasal proteosome-based adjuvants has a potential to treat AD.

Authors/Disclosures
Ron CIalic PRESENTER	No disclosure on file
Oleg Butovsky, PhD (Brigham and Women's Hospital/Harvard Medical)	No disclosure on file
	No disclosure on file
Stefan Braune (Gemeinschaftspraxis)	Stefan Braune has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NeuroTransData. Stefan Braune has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Stefan Braune has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for NeuroTransData.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Howard L. Weiner, MD (Brigham and Women'S Hospital)	Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Weiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Tiziana Life Sciences. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for vTv Therapeutics. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Medday Pharmaceuticals. Dr. Weiner has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for vTv Therapeutics. Dr. Weiner has stock in vTv Therapeutics. The institution of Dr. Weiner has received research support from National Institute of Health. The institution of Dr. Weiner has received research support from National MS Society. The institution of Dr. Weiner has received research support from Genzyme Corp. The institution of Dr. Weiner has received research support from Genentech, Inc. . The institution of Dr. Weiner has received research support from Verily Life Sciences LLC. The institution of Dr. Weiner has received research support from EMD Serono, Inc..

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