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Fig. 2 | Alzheimer's Research & Therapy

Fig. 2

From: Partial reduction of amyloid β production by β-secretase inhibitors does not decrease synaptic transmission

Fig. 2

Amyloid β secretion and synaptic transmission upon β-secretase inhibition. Primary rat neurons treated with 0, 0.04, 0.3, and 3 μM of three different BACE inhibitors for 4 days. Thereafter, Aβ secretion to the cell-conditioned media was measured using immunochemiluminescence techniques. Synaptic transmission was measured using an optical electrophysiology platform. a All concentrations tested for lanabecestat equally decreases Aβ40 (I) and Aβ42 (II). All concentrations also decrease synaptic transmission between neurons (III). b While 0.04 μM LY286721 does not affect Aβ40 secretion, both 0.3 μM and 3.0 μM decreases secretion of Aβ40 (I). Of the three doses tested, only 3.0 μM LY286721 significantly decreases Aβ42 (II) and decreases synaptic transmission between neurons (III). c Already 0.04 μM BACE inhibitor IV decreases secretion of Aβ40 (I) and Aβ42 (II) and both 0.3 μM and 3.0 μM BACE inhibitor IV decreases the secretion further (III). Whereas 0.04 μM BACE inhibitor IV increases synaptic transmission, 0.3 μM has no effect and 3.0 μM decreases synaptic transmission. Both secretion and synaptic transmission normalized with DMSO control and presented as percentage. Bars represent mean +/− SEM. n = 3 from 3 individual primary cortical cultures for secretion data, n = 12 separate experiments from 2 individual primary cortical cultures for synaptic transmission data. Student’s t test is performed between the controls and each concentration. *p ≤ 0.05, **p ≤ 0.01, *** p ≤ 0.001, ****p ≤ 0.0001

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