Figure 5.

A twofold increase in soluble αSyn is associated with a selective decrease in vesicular proteins in AD. A, Western blot (WB) analysis of brain extracts from 17-month-old Tg2576 (APP Tg) and 10-month-old TgG2.3-A53T (αSyn Tg) brain tissue using infrared-conjugated secondary antibodies shows a selective reduction in synapsins in αSyn Tg. Rab3, synaptophysin, and actin levels were unchanged in both lines. B, Quantification of protein levels detected in both lines revealed specific decreases in synapsins in αSyn Tg mice (n = 3/group). C, Scatterplot of soluble αSyn levels in the ITG of subjects with AD. Measurements reflect the quantification of αSyn by WB after SDS-PAGE using the antibody LB509. Selected AD subjects were chosen to compose two groups (n = 3 per group) whose soluble αSyn ratio equaled 2. They are referred to as AD-High and AD-Normal and are indicated by filled red circles. D, Linear regression depicting the relationship between episodic memory and the levels of monomeric αSyn in the IC fraction measured by SDS-PAGE. Filled circles indicate specimens selected for analyses of vesicular presynaptic proteins (see Figs. 3 and 4). Note that the AD subjects with a twofold elevated αSyn are more impaired than AD subjects with lower αSyn expression. E, Quantitative WB analysis of brain extracts from AD brain tissue with normal (AD-Normal) or high (AD-High) (2-fold increase) αSyn-IC levels shows a reduction in synapsins and complexins but not Rab3 or synaptophysin. F, Quantification confirms the observed changes in B. Values represent mean ± SD (n = 3). G, Regression analyses between total synapsin protein expression and “monomeric” αSyn in all AD cases (n = 24) indicated a negative correlation (Spearman rho).