Aβ42 O (1µM) Surface 1 Total 1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A...

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0 25 50 75 100 125 C ont A 42 O Surface 1 /Total (% C ont) Aβ42 O (1µM) Surface 1 Total 1 A B ** 25 Aβ42 M FITC- Aβ42 M Aβ42 O FITC- Aβ42 O 15 10 Aβ42 M Aβ42 Di Aβ42 Tr i Aβ42 Te t - + C Supplemental Fig. S

Transcript of Aβ42 O (1µM) Surface 1 Total 1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A...

Page 1: Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental.

0

25

50

75

100

125

Cont

A42O

Su

rfac

e

1 /

To

tal

(% C

on

t)

Aβ42O (1µM)

Surface 1

Total 1

A B

**

25

Aβ42M

FITC-Aβ42MAβ42O

FITC-Aβ42O

1510

Aβ42M

Aβ42Di

Aβ42Tri

Aβ42Tet

- +

C

Supplemental Fig. S1

Page 2: Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental.

0 20 40 60 80 1000.0

0.1

0.2

0.3

0.4Biotin-A42M

Biotin-A42O

Biotin-A42F

Biotin-A42 (nM)

Sp

ecifi

c B

ind

ing

(O

D)

#

#

#

Supplemental Fig. S2

Page 3: Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental.

Vinculin

Actin

Vinculin

Actin

Aβ42O (µM)

B - 0.25 2 - 0.25 2

2h 4h

Cy

toF

C

C

***

Tubulin

Vinc

Talin

Tubulin

Vinc

Talin

- + A

FC

Cy

to

Aβ42O

Supplemental Fig. S3

0

25

50

75

100

125

Cont

A42O (0.25M)A42O (2M)

FA

Vin

culin

(%

Co

nt)

D

0

25

50

75

100

125

WTAPP/PS1

Fo

cal V

inc

Are

a(%

WT

)

APP/PS1 WT

Scale b

ar 30μm 0

25

50

75

100

125

WTAPP/PS1

Fo

cal V

inc

Siz

e(%

WT

)

**

E

*

Fo

ca

l V

inc

uli

n /

C

yto

so

lic

Vin

cu

lin

FC V

incu

lin (%

Con

t)

0

25

50

75

100

125

Cont

A42O (0.25M)A42O (2M)

FA

Vin

culin

(%

Co

nt)

Page 4: Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental.

Cy

toF

C

Aβ42O - + + -

- - + + Cof siR

Cofilin

P-Cof

Vinculin

Cofilin

P-Cof

Vinculin

A

0

25

50

75

100

125

Cont siR (Veh)

Cont siR (A42O)Cof siR (Veh)

Cof siR (A42O)

FA

Vin

c (%

Co

nt)

B

**

Supplemental Fig. S4

FC V

inc

(% C

ont)

0

25

50

75

100

125

Cont siR (Veh)

Cont siR (A42O)Cof siR (Veh)

Cof siR (A42O)

FA

Vin

c (%

Co

nt)

Page 5: Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental.

NC (n=4) AD (n=5)

Gender 2M & 2F 2M & 3F

Age Range 82-95 82-96

Average Age (+SD) 88.75 + 6.70 88.4 + 5.94

PMI Range (h) 3.87-8.6 3.0-7.8

Average PMI (+SD) 5.63 + 2.15 4.46 + 1.93

Supplemental Fig. S5

Page 6: Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental.

Vehicle Aβ42O (1uM)

Nox inhibitor HUTS-4 MAB1965Vehicle

H2D

CF

Supplemental Fig. S6

A

Page 7: Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental.

42O

+1

Ig

GA

β42

OC

on

tro

l

Annexin VDAPI

PI / DAPI

Cont A

1 Ig

G

+

A

0

20

40

60

Lat

e A

po

pto

tic

(%)

0

5

10

15

20

25

Ear

ly A

po

pto

tic

(%)

B C

**

H

Control A42O A42O + MAB1965

PI

D

Supplemental Fig. S6 Continued

Page 8: Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental.

P-Cof

Actin

Aβ42O - + + +

Ve

h

Ve

h

MA

B1

96

5

Tro

lox

IP: 14-3-3SSH1

B

Ly

sa

teCof

SSH1

SSH1

Be

ad

s

14

-3-3

Supplemental Fig. S7

A

Aβ42O

C

be

ad

s

- - +

Cof

SS

H1

SS

H1

IP:

SSH1

Cof Ly

sa

teIP

D

0

100

200

300

400

Cont

A42O

SS

H1-

Co

f C

om

ple

x(%

Co

nt)

**

Be

ad

s

14

-3-3

IP:

14-3-3

Page 9: Aβ42 O (1µM) Surface  1 Total  1 A B ** 25 A β42 M FITC- A β42 M A β42 O FITC- A β42 O 15 10 A β42 M A β42 Di A β42 Tri A β42 Tet - + C Supplemental.

Supplemental Fig. S8

Cofilin

Cofilin

Actin

Actin

WT

WT

Cofili

n +/

-Cof

ilin

+/-

HIP

PO

CT

XWT

GF

AP

DA

PI

PS

D9

5D

AP

IS

yn

ap

sin

I

Cofilin+/-

A

DG

CA1

CA3

Scale bar

300μm

CA3

SL

SL

B