Fig. 1

Alterations of CSF CAP2 level in dementia patients and effects of CAP2 downregulation on tau. a CAP2 levels in clinical groups. #P < 0.001 *P < 0.05. b-d CAP2 downregulation promotes tau phosphorylation at Thr181. b Experimental paradigm: primary hippocampal neurons at 10 days in vitro (DIV 10) were transduced with rAAV expressing a shRNA targeting CAP2 (shCAP2) or with a control sequence (scrCAP2). Analysis was performed at DIV 17. c Representative Western blots showing the protein levels of CAP2, mCherry to confirm the transduction, and actin as a loading control in homogenate of hippocampal cultures transduced with shCAP2 (or scrCAP2). Quantification of optical density (OD) shows that CAP2 is significantly downregulated (scrCAP2 100 ± 21.34, shCAP2 37.73 ± 8.509; two-tailed paired t-test: **P = 0.0040, n = 13). d Representative Western blots for p-tau181, total tau, and mCherry in lysates of hippocampal neurons transduced with shCAP2 or scrCAP2. The p-tau 181/t-tau ratio was significantly increased when CAP2 was down-regulated (158.8 ± 30.04 versus 100 ± 11.94, Wilcoxon test: *P = 0.0210, n = 12). All data are presented as percentage of control (scrCAP2) and expressed as mean ± SE. AD, Alzheimer’s disease; DLB, dementia with Lewy bodies; FTD, frontotemporal dementia; HC, healthy controls; prod-AD, prodromal AD