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. 2016 Jan 29;30(3):272–275. doi: 10.1097/WAD.0000000000000130

FIGURE 2.

FIGURE 2

Chorein deficiency and its impact on amyloid processing. A, Family tree, with the proband indicated by black arrow. The proband and 2 of 3 of her children presented with neuropsychiatric disorders (black symbols; clinical details in the text). Clinical profile of other family members remained undetermined (white symbols). B, Illustration of the results of genetic analysis. Deleted exons in chorein are marked with gray asterisk. The alternative splicing site is marked with black asterisk, and the exon 69 (skipped in the canonical form of chorein) is shadowed. C–F, In vitro chorein knockdown system. The neuronal SH-SY5Y cells were transfected with specific, chorein-targeting siRNA (white bars) or negative control siRNA (black bars). Expression of chorein (C), as well as APP, PSEN1, PSEN2, and SORL1 (E) was assessed by quantitative PCR and expressed as a percentage of its respective negative control; chorein knockdown had no impact on the viability/proliferation of SH-SY5Y cells (D); concentration of Aβ40, but not Aβ42, was significantly decreased in supernatants from SH-SY5Y cells upon chorein knockdown (F); concentration of Aβ40 was low in the cerebrospinal fluid of the proband, as compared with mean reference values previously reported for healthy controls (black arrow and dashed line) and demented patients carrying PSEN1 pathogenic mutations (gray arrow and dashed line) (G). For quantitative PCR analysis 7 (n=7; C) or 4 (n=4; E) independent experiments were performed. For cell counting (D) and measurement of Aβ concentrations (F), 5 independent experiments were performed (n=5). All of the values in the panels (C–E) are presented as percentages of the respective control groups (means±SEM). The significance of the differences (chorein knockdown vs. control) was tested by the 2-tailed Mann-Whitney nonparametric test (E), or by the 2-tailed paired t test for the sets of data following normal distribution (C, D, F; normal distribution confirmed by Kolmogorov-Smirnov test). The difference between the means were considered significant if P<0.05. NS indicates statistically not significant; **P<0.01.