Table 1.

Effects of ELAVL4 expression manipulation on APP and tau phenotypes

	APP Phenotypes			Tau Phenotypes

	RNA	Protein	Processing	RNA	Protein

Knock out
fAD^corr ELAVL4 KO	Total ↓ 97.9 % n.s.	Total ↑100.1 % n.s.	Aβ42/40 ↑ 104.1 % n.s.	↑ 111.9 % ^****	Total tau ↑ 124.8 % ^*
	695 ↓ 97.2 % n.s.		Aβ42 ↓ 90.0 % n.s.		P-tau181 ↑ 105.2 % ^*
	751 ↑ 127.6 % ^*		Aβ40 ↓ 86.4 % ^*
	770 ↑ 104.4 % n.s.		Aβ38 ↓ 90.8 % n.s.
fAD ELAVL4 KO	Total ↑112.0 % n.s.	Total ↓ 79.7 % ^**	Aβ42/40 ↓ 97.7 % n.s.	↓ 93.2 % ^*	Total tau ↑ 106.8 % n.s.
	695 ↑100.2 % n.s.		Aβ42 ↓ 84.3 % ^***		P-tau181 ↑ 104.4 % ^*
	751 ↑ 121.9 % ^**		Aβ40 ↓ 86.6 % ^**
	770 ↑ 213.5 % ^***		Aβ38 ↓ 82.2 % ^**
Over Expression
fAD^corr ELAVL4-sv2	Total ↑ 114.3 % ^*	Total ↑ 114.7 % ^**	Aβ42/40 ↓ 90.1 % ^**	↑ 103.9 % n.s.	Total tau ↓ 94.0 % n.s.
	695 ↑ 110.4 % ^**		Aβ42 ↓ 94.2 % n.s.		P-tau181 ↓ 89.3 % ^*
	751 ↓ 66.8 % ^****		Aβ40 ↑ 104.6 % n.s
	770 ↓ 23.7 % ^****		Aβ38 ↑ 108.9 % n.s
fAD ELAVL4-sv2	Total ↑ 118.9 % ^*	Total ↑ 210.9 % ^****	Aβ42/40 ↓ 87.4 % ^****	↑105.5 % n.s.	DAKO ↓ 99.7 % n.s.
	695 ↑ 126.8 % ^**		Aβ42 ↓ 85.4 % n.s		P-tau181 ↓ 90.6 % ^*
	751 ↓ 75.2 % ^***		Aβ40 ↓ 97.4 % n.s
	770 ↓ 23.5 % ^****		Aβ38 ↓ 96.2 % n.s.
fAD^corr ELAVL4-sv1	Total ↑ 113.6 % ^*	Total ↓ 85.1 % ^**	Aβ42/40 ↓ 88.1 % ^***	↑ 110.0 % ^*	Total tau ↑ 100.4 % n.s.
	695 ↑ 112.5 % ^**		Aβ42 ↑ 110.7 % n.s		P-Tau181 ↓ 83.7 % ^***
	751 ↓ 67.5 % ^****		Aβ40 ↑ 127.1 % ^**
	770 ↓ 33.1 % ^****		Aβ38 ↑ 122.4 % ^**
fAD ELAVL4-sv1	Total ↑102.1 % n.s.	Total ↑ 145.9 % n.s.	Aβ42/40 ↓ 83.9 % ^****	↑ 114.0 % ^*	Total tau ↑ 119.4 % ^**
	695 ↑ 107.0 %		Aβ42 ↓ 94.4 % n.s		P-tau181 ↓ 83.3 % ^****
	751 ↓ 75.5 % ^**		Aβ40 ↑ 111.5 % n.s.
	770 ↓ 33.6 % ^****		Aβ38 ↑ 103.6 % n.s.
*Rescue in ELAVL4* KO**
fAD^corr *ELAVL4* KO ELAVL4-sv2	Total ↑ 105.7 % n.s.	Total ↑ 140.8 % ^****	Aβ42/40 ↑ 100.8 % n.s	↓ 94.2 % n.s	DAKO ↓ 86.7 % n.s.
	695 ↑ 110.1 % n.s.		Aβ42 ↓ 85.0 % n.s.		P-tau181 ↓ 78.4 % ^****
	751 ↓ 54.7 % ^****		Aβ40 ↓ 84.6 % n.s.
	770 ↓ 17.0 % ^***		Aβ38 ↓ 96.0 % n.s.
fAD ELAVL4 KO ELAVL4-sv2	Total ↑ 107.6 % n.s.	Total ↑ 277.6 % ^**	Aβ42/40 ↓ 89.1 % ^***	↑106.3 % n.s.	DAKO ↓ 85.7 % n.s.
	695 ↑ 103.9 % n.s.		Aβ42 ↓ 92.4 % n.s		P-tau181 ↓ 85.2 % ^***
	751 ↓ 53.5 % ^****		Aβ40 ↑ 103.6 % n.s.
	770 ↓ 14.5 % ^****		Aβ38 ↑ 112.6 % n.s.
fAD^corr ELAVL4 KO ELAVL4-sv1	Total ↑ 103.9 % n.s.	Total ↑ 110.7 % n.s.	Aβ42/40 ↓ 93.0 % ^*	↓ 95.4 % n.s	DAKO ↓ 91.6 % n.s.
	695 ↑ 107.7 % n.s.		Aβ42 ↓ 95.4 % n.s.		P-tau181 ↓ 70.4 % ^****
	751 ↓56.7 % ^****		Aβ40 ↑ 104.4 % n.s
	770 ↓ 47.0 % ^**		Aβ38 ↓ 99.6 % n.s.
fAD ELAVL4 KO ELAVL4-sv1	Total ↑ 108.6 % n.s.	Total ↑ 241.5 % ^*	Aβ42/40 ↓ 88.4 % ^***	↑ 111.3 % ^**	Total tau ↓ 89.1 % n.s.
	695 ↑ 106.6 % n.s.		Aβ42 ↓ 95.3 % n.s		P-tau181 ↓ 81.8 % ^****
	751 ↓ 58.3 % ^****		Aβ40 ↑ 108.9 % n.s.
	770 ↓ 19.7 % ^****		Aβ38 ↑ 113.3 % n.s.

NOTE. Summarized data. For all conditions: per condition, three replicates from three independent differentiations were used. Total protein determined by BCA was used to normalize measured values for individual Aβ species. For KO conditions: changes relative to CRISPR control line, P-value calculated with ↑ tests. For OE and rescue conditions: changes relative to empty vector control, P-values calculated with Dunnett’s multiple comparison that followed after ANOVA test.

P < 0.05

^**

P < 0.01

^***

P < 0.001

^****

P < 0.0001