Animal experiment:

Sprague Dawley [Crl:CD(SD)] rats (10 per sex per group), appr 7 weeks of age, are given 0 (vehicle only), 10, 30, or 100 mg/kg LY2811376 by daily oral gavage. Vehicle consists of 1% (w/v) hydroxyethylcellulose, 0.25% (v/v) polysorbate 80, and 0.05% (v/v) Dow Corning Antifoam 1510-US in reverse osmosis water. At necropsy after 3 months of treatment, tissues are immersion fixed in 10% neutral-buffered formalin (brain) or modified Davidson's solution (eyes) and then processed by routine methods to paraffin block and hematoxylin-eosin (H&E)-stained histologic slides. From selected animals given 100 mg/kg on a subsequent investigative study, eyes are fixed in modified Karnovsky's solution, processed routinely into epoxy resin, and then ultrathin sections stained with uranyl acetate and Sato's lead citrate are examined in a transmission electron microscope. In a separate study, BACE1 knock-out mice (B6.129-Bace1tm1Pcw/J) are given 0 or 100 mg/kg LY2811376 by daily oral gavage for 9 weeks, and then necropsied tissues are collected and examined by light microscopy as described above for the rat toxicology study.

LY2811376 is a non-peptidic inhibitor of BACE1.
Beta-secretase 1 (BACE1) is an aspartic-acid protease that cleaves the amyloid precursor protein (APP) into amyloid-βpeptide (Aβ), which plays a critical role in Alzheimer's disease (AD).
In recombinant enzyme assays, LY2811376 inhibited hBACE1 with IC50 values of 249 nM and 239 nM against a larger chimeric protein substrate and a small synthetic peptide, respectively. In a human embryonic kidney cell line overexpressed APP, LY2811376 decreased Aβ secretion with EC50 value of 300 nM in a concentration-dependant way [1]. In SH-SY5Y cells, LY2811376 reduced Aβ1-40 and Aβ1-42 secreted to the cell medium while increased the level of Aβ5-40 [2].
In the APPV717F mouse, LY2811376 significantly reduced Aβ, as well as sAPP and C99, the cleavage products of APP by BACE1 [1]. In a healthy population (n =18), LY2811376 (30 mg, 90 mg) increased Aβ5-40 and Aβ5-X in a dose-dependant way, while Aβ1-34 reduced in a same way. These results suggested that LY2811376 inhibited N-terminally truncated Aβ peptides in a BACE1-independent pathway [2].
References:
[1]. May PC, Dean RA, Lowe SL, et al. Robust Central Reduction of Amyloid-  in Humans with an
Orally Available, Non-Peptidic  -Secretase Inhibitor. J Neurosci, 2011, 31(46): 16507-16516.
[2]. Portelius E, Dean RA, Andreasson U, et al. β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) inhibitor treatment induces Aβ5-X peptides through alternative amyloid precursor protein cleavage. Alzheimers Res Ther, 2014, 6(5-8): 75.