SAR228810: an antibody for protofibrillar amyloid β peptide designed to reduce the risk of amyloid-related imaging abnormalities (ARIA)

Table 3 Antibody dose-dependent prevention of amyloid accumulation and inflammation in APPSL transgenic mice

Treated groups	Ctrl-IgG1	SAR255952			3D6
Dose (mg/kg)	10	1	3	10	3	10
Biochemical cortical Aβ
Pan-Aβ μg/g tissue	23.7 ± 1.7	25.1 ± 1.8	17.8 ± 1.7	14.0 ± 1.4	24.3 ± 2.3	13.5 ± 3.4
% reduction vs. Ctrl-IgG1		+6%	–25%	−41%	+3%	−43%
% reduction vs. Ctrl-IgG1		NS	NS	p < 0.05	NS	p < 0.001
Aβ42 μg/g tissue	7.62 ± 0.58	8.86 ± 0.74	6.62 ± 0.68	5.28 ± 0.77	8.49 ± 0.84	4.92 ± 1.65
% reduction vs. Ctrl-IgG1		+16%	−13%	−31%	+11%	−35%
% reduction vs. Ctrl-IgG1		NS	NS	NS	NS	NS
Cystatin F mRNA hippocampus	4.47 ± 0.35	4.27 ± 0.35	2.35 ± 0.29	0.99 ± 0.07	4.99 ± 0.37	2.19 ± 0.49
% reduction vs. Ctrl-IgG1		−4%	−47%	−78%	+12%	−51%
% reduction vs. Ctrl-IgG1		NS	p < 0.05	p < 0.001	NS	p < 0.05
Aβ immunohistochemistry
Total area cortex (μm²)	382,388	339,950	188,729	83,495	387,344	151,764
SEM	29,945	44,091	19,154	14,776	53,255	31,968
% reduction vs. Ctrl-IgG1		−11%	−51%	−78%	+1%	−60%
% reduction vs. Ctrl-IgG1		NS	p = 0.013	p < 0.0001	NS	p = 0.003
Total area hippocampus (μm²)	103,417	66,849	42,794	20,646	77,838	60,972
SEM	11,020	13,435	4546	4329	9786	8192
% reduction vs. Ctrl-IgG1		−35%	−59%	−80%	−25%	−41%
% reduction vs. Ctrl-IgG1		NS	p = 0.0123	p < 0.0001	NS	p = 0.0116
Plasma Aβ40 pg/ml	175 ± 31	198 ± 20	201 ± 34	211 ± 27	680 ± 130	999 ± 142

For the different parameters, values represent mean ± standard error of the mean (SEM) unless indicated otherwise
Aβ amyloid β, NS not significant

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