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Lars Lannfelt
Christer M�ller
Hans Basun
Gunilla Osswald
Dag Sehlin
Andrew Satlin
Veronika Logovinsky
P�r Gellerfors
Perspectives on future Alzheimer therapies: amyloid-� protofibrils - a new target for immunotherapy with BAN2401 in Alzheimer�s disease
2014, :. doi:
� 2014 Lannfelt et al.; licensee BioMed Central Ltd.
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1 0 0 1 538.5830078125 498.217010498 cm
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-0.5099999905 0 0.5102499723 -6.0095000267 re
B*
Q
q
1 0 0 1 56.6930007935 492.2080078125 cm
0 0 m
0.5099999905 0 -0.5102400184 6.0095000267 re
B*
Q
q
1 0 0 1 538.5830078125 492.2080078125 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 480.1889953613 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 480.1889953613 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 468.2269897461 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 468.2269897461 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 456.2080078125 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 456.2080078125 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 444.1889953613 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 444.1889953613 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 432.2269897461 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 432.2269897461 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 420.2080078125 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 420.2080078125 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 408.1889953613 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 408.1889953613 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 396.2269897461 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 396.2269897461 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 384.2080078125 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 384.2080078125 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 372.1889953613 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 372.1889953613 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 360.2269897461 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 360.2269897461 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 348.2080078125 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 348.2080078125 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 336.1889953613 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 336.1889953613 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 324.2269897461 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 324.2269897461 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 312.2080078125 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 312.2080078125 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 300.1889953613 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 300.1889953613 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 288.2269897461 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 288.2269897461 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 276.2080078125 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 276.2080078125 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 264.1889953613 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 264.1889953613 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 252.2270050049 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 252.2270050049 cm
0 0 m
0 -2.5510001183 l
-0.5099999905 -2.5510001183 l
-0.5099999905 0 l
B*
Q
q
1 0 0 1 538.5830078125 249.675994873 cm
0 0 m
-0.057 -0.6800000072 l
-0.2479999959 -2.2000000477 -1.7300000191 -3.7400000095 -3.2880001068 -3.9119999409 c
-4.0250000954 -3.9690001011 l
-4.0250000954 -3.4579999447 l
-3.4019999504 -3.4019999504 l
-1.9950000048 -3.2750000954 -0.7689999938 -1.9440000057 -0.5669999719 -0.5669999719 c
-0.5099999905 0 l
B*
Q
q
1 0 0 1 534.5570068359 245.7070007324 cm
0 0 m
-473.8389892578 0 l
-473.8389892578 0.5099999905 l
0 0.5099999905 l
B*
Q
q
1 0 0 1 60.7179985046 245.7070007324 cm
0 0 m
-0.7369999886 0.057 l
-2.2950000763 0.2290000021 -3.7769999504 1.7680000067 -3.9690001011 3.2880001068 c
-4.0250000954 3.9690001011 l
-3.5150001049 3.9690001011 l
-3.4579999447 3.4019999504 l
-3.256000042 2.0239999294 -2.0299999714 0.6930000186 -0.6240000129 0.5669999719 c
0 0.5099999905 l
B*
Q
q
1 0 0 1 56.6930007935 249.675994873 cm
0 0 m
0 2.5510001183 l
0.5099999905 2.5510001183 l
0.5099999905 0 l
B*
Q
BT
/F1 1 Tf
13 0 0 13 60.7181015015 690.6895751953 Tm
0 0 0 0 k
0.1163000017 Tc
0 Tw
(REVIEW) Tj
/F2 1 Tf
22.7999000549 0 0 24.0000991821 56.6929016113 652.7053222656 Tm
0 0 0 1 k
0 Tc
[(Perspectives) -305.799987793 (on) -299.5 (future) -302.700012207 (Alzheimer) -302.200012207 (therapies:) ] TJ
0 -1.0842000246 TD
(amyloid-) Tj
/F3 1 Tf
3.6452999115 0 TD
() Tj
/F2 1 Tf
0.8529000282 0 TD
[(protofibrils) -306.299987793 (-) -299.700012207 (a) -299.299987793 (new) -300.200012207 (target) -302.8999938965 (for) ] TJ
-4.4981999397 -1.0819000006 TD
[(immunotherapy) -305.3999938965 (with) -301.5 (BAN2401) -301.6000061035 (in) -300.6000061035 (Alzheimer) ] TJ
/F4 1 Tf
18.5944004059 0 TD
<92> Tj
/F2 1 Tf
0.1342999935 0 TD
(s) Tj
-18.7285995483 -1.0842000246 TD
(disease) Tj
/F5 1 Tf
10.4498996735 0 0 11.0001001358 56.6929016113 550.7147827148 Tm
[(Lars) -301 (Lannfelt) ] TJ
7.8372001648 0 0 7.3326997757 109.5874023438 555.5905151367 Tm
(1,2*) Tj
10.4498996735 0 0 11.0001001358 121.4362030029 550.7147827148 Tm
[(,) -300.6000061035 (Christer) -303.1000061035 <4DF66C6C6572> ] TJ
7.8372001648 0 0 7.3326997757 187.0865936279 555.5905151367 Tm
(2) Tj
10.4498996735 0 0 11.0001001358 190.8849945068 550.7147827148 Tm
[(,) -300.6000061035 (Hans) -300.700012207 (Basun) ] TJ
7.8372001648 0 0 7.3326997757 244.1763000488 555.5905151367 Tm
(1,2) Tj
10.4498996735 0 0 11.0001001358 252.9636993408 550.7147827148 Tm
[(,) -300.6000061035 (Gunilla) -307.6000061035 (Osswald) ] TJ
7.8372001648 0 0 7.3326997757 324.2267150879 555.5905151367 Tm
(2) Tj
10.4498996735 0 0 11.0001001358 327.9684143066 550.7147827148 Tm
[(,) -300.6000061035 (Dag) -303.799987793 (Sehlin) ] TJ
7.8372001648 0 0 7.3326997757 378.311706543 555.5905151367 Tm
(1) Tj
10.4498996735 0 0 11.0001001358 382.1101074219 550.7147827148 Tm
[(,) -300.6000061035 (Andrew) -302 (Satlin) ] TJ
7.8372001648 0 0 7.3326997757 445.4927978516 555.5905151367 Tm
(3) Tj
10.4498996735 0 0 11.0001001358 449.2912902832 550.7147827148 Tm
(,) Tj
-37.5694999695 -1.2730000019 TD
[(Veronika) -302.3999938965 (Logovinsky) ] TJ
7.8372001648 0 0 7.3326997757 142.0157012939 541.5872802734 Tm
(3) Tj
10.4498996735 0 0 11.0001001358 148.87550354 536.7116699219 Tm
[(and) -303.8999938965 <50E472> -302.799987793 (Gellerfors) ] TJ
7.8372001648 0 0 7.3326997757 222.9732055664 541.5872802734 Tm
(2) Tj
/F1 1 Tf
10.3000001907 0 0 10.3000001907 63.212600708 498.2171936035 Tm
(Abstract) Tj
/F5 1 Tf
10.0001001358 0 0 10.0001001358 63.212600708 480.1889038086 Tm
-0.0333000012 Tc
[(T) 5.1999998093 (h) -1.2000000477 (e) -268.6000061035 (s) 1.8999999762 (ymptomatic) -265.299987793 (drugs) -264.6000061035 (c) 1.2000000477 (urrent) ] TJ
11.6899995804 0 TD
-0.0328000002 Tc
[(ly) -264.799987793 (on) -267.1000061035 (the) -268.1000061035 (m) 2.5 (arket) -269.3999938965 (f) 0.400000006 (or) -263.3999938965 (Alzh) 5 (ei) 5.0999999046 (mer) ] TJ
/F6 1 Tf
11.3271999359 0 TD
0 Tc
<92> Tj
/F5 1 Tf
0.1360999942 0 TD
-0.0357999988 Tc
[(s) -267.1000061035 (d) -5 (is) -6.3000001907 (ease) -271.1000061035 (\(AD) -3.0999999046 (\)) -269 (h) -3.7000000477 (ave) -271.1000061035 (no) -270.1000061035 (e) -4.6999998093 (f) -2.5999999046 (fe) -4.6999998093 (ct) -272.3999938965 (on) ] TJ
12.2398996353 0 TD
-0.0346000008 Tc
[(disease) -269.8999938965 (p) -3.7999999523 (rogression,) -271.1000061035 (a) -1.5 (nd) -270.299987793 (this) ] TJ
-35.3931999207 -1.1962000132 TD
-0.0339000002 Tc
[(creates) -270.799987793 (a) -267.200012207 (large) -269.200012207 (u) 4.1999998093 (nmet) -270.5 (medical) -273.799987793 (n) 3.9000000954 (eed.) -270.3999938965 (The) -269.200012207 (t) 1.6000000238 (ype) -269.200012207 (o) -1.7999999523 (f) -272.799987793 (d) 2.5 (rug) -269.6000061035 (t) 1.6000000238 (hat) -270.5 (h) 3.9000000954 (as) ] TJ
23.5501003265 0 TD
-0.0335000008 Tc
[(develo) 4.3000001907 (ped) -269.200012207 (m) -3.9000000954 (o) 4.3000001907 (s) 1.7000000477 (t) -270.1000061035 (r) -3.2999999523 (a) 5.3000001907 (p) -2.7000000477 (idly) -265.5 (in) -267.8999938965 (the) -268.799987793 (l) -1.2000000477 (ast) -264.3999938965 (d) -2.7000000477 (ecade) -268.799987793 (i) 4.4000000954 (s) -270.3999938965 (i) -1.2999999523 (mmuno) 4.3000001907 (th) 4.3000001907 (erapy:) ] TJ
-23.5501003265 -1.2019000053 TD
-0.0340000018 Tc
[(va) 4.8000001907 (ccines) -270.8999938965 (and,) -270.5 (especially,) -270.5 (p) -3.2000000477 (assiv) 4.8000001907 (e) -269.299987793 (vaccina) ] TJ
14.6323003769 0 TD
-0.0362000018 Tc
[(tio) -4.0999999046 (n) -270.5 (w) -4.1999998093 (i) -3.9000000954 (th) -270.5 (mo) -4.0999999046 (no) -4.0999999046 (cl) -3.9000000954 (on) -4.0999999046 (al) -270.3999938965 (an) -4.0999999046 (tib) -5.4000000954 (o) 1.6000000238 (d) -5.4000000954 (i) -3.9000000954 (es.) -272.700012207 (A) -3.0999999046 (nt) -6.3000001907 (ib) -5.4000000954 (od) ] TJ
15.4996995926 0 TD
-0.0342999995 Tc
[(ies) -271.200012207 (a) -1.2000000477 (re) -269.6000061035 (attractive) -269.6000061035 (drugs) -271.200012207 (a) -1.2000000477 (s) -271.200012207 (t) 1.2000000477 (hey) -271.8999938965 (c) 0.200000003 (an) -268.6000061035 (be) -269.6000061035 (made) ] TJ
-30.1320991516 -1.2019000053 TD
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[(highly) -265.700012207 (specific) -271.299987793 (for) -264.299987793 (t) -3.7999999523 (heir) -269.8999938965 (target) -264.6000061035 (and) -269.3999938965 (o) -1.6000000238 (f) 5.1999998093 (t) 1.7999999523 (en) -268.1000061035 (with) -268 (few) -268.1000061035 (s) -4.1999998093 (ide) -269 (e) 3.0999999046 (ffects.) ] TJ
22.9095001221 0 TD
-0.0342000015 Tc
[(Data) -273.200012207 (from) -271 (recent) -265.1000061035 (clinical) -268.3999938965 (AD) -267.8999938965 (tr) -4 (ials) -271.1000061035 (indicate) -269.5 (that) -270.799987793 (a) -267.5 (t) 1.2999999523 (r) -4 (e) 2.5999999046 (atment) ] TJ
-22.9095001221 -1.1962000132 TD
-0.0337999985 Tc
[(effect) -270.3999938965 (by) -271.3999938965 (immuno) 4 (therapy) -271.3999938965 (i) 4.0999999046 (s) -270.700012207 (p) -3 (o) 4 (s) -4.3000001907 (si) 4.0999999046 (bl) 4.0999999046 (e,) -270.299987793 (pro) 4 (v) -0.6999999881 (idin) 4 (g) -269.5 (hope) -269.1000061035 (f) -0.6000000238 (or) -270 (a) -267.1000061035 (n) -1.7000000477 (ew) ] TJ
23.7087993622 0 TD
-0.0335999988 Tc
[(generati) 4.3000001907 (on) -267.8999938965 (of) -266.799987793 (drugs.) -264.5 (The) -268.8999938965 (f) -0.400000006 (i) 4.3000001907 (r) -3.4000000954 (st) -270.200012207 (a) 5.1999998093 (n) -1.5 (ti-amyloi) 4.3000001907 (d) -2.7999999523 (-beta) -272.6000061035 (\() 5.3000001907 (anti-A) ] TJ
/F7 1 Tf
20.0067996979 0 TD
0 Tc
() Tj
/F5 1 Tf
0.5045999885 0 TD
(\)) Tj
-44.220199585 -1.2019000053 TD
-0.0326000005 Tc
[(va) 6.1999998093 (cci) 5.3000001907 (n) -0.5 (e) -267.8999938965 (d) 3.7999999523 (eve) 4.1999998093 (l) -0.3000000119 (o) 5.1999998093 (p) -1.7999999523 (e) 4.1999998093 (d) -268.299987793 (by) -264.6000061035 (Elan) 5.1999998093 (,) -269.1000061035 (A) 0.5 (N1) 4.1999998093 (79) 4.1999998093 (2,) -269.1000061035 (w) 5.0999999046 (a) 0.5 (s) -269.5 (h) -0.5 (al) 5.3000001907 (ted) -268.299987793 (i) 5.3000001907 (n) -272.6000061035 (p) 3.7999999523 (hase) -267.8999938965 (2) -267.8999938965 (b) 3.7999999523 (ecau) ] TJ
24.2870998383 0 TD
-0.0348000005 Tc
[(se) -270.1000061035 (of) -273.700012207 (asep) -4 (tic) -266.799987793 (m) -5.1999998093 (eningoence) -3.7000000477 (phal) ] TJ
11.6162996292 0 TD
0.2355999947 Tc
[(i) 267.8999938965 (t) 271.1000061035 (i) 273.5 (s) 265.1000061035 (.H) 271 (o) 273.3999938965 (w) 267.6000061035 (e) 272.3999938965 (v) 268.700012207 (e) 266.700012207 (r) 271.5 (,i) 267.8999938965 (naf) 268.799987793 (o) 267.700012207 (l) 273.5 (l) 267.8999938965 (o) 267.700012207 (w) 273.299987793 (-) 265.799987793 (u) 273.700012207 (p) ] TJ
-35.9034004211 -1.2019000053 TD
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[(study,) -259.6000061035 (patients) -260 (with) -257.3999938965 (ant) -4.5 (i) 3.5 (body) -255 (r) -4.1999998093 (e) 2.4000000954 (sponse) -258.3999938965 (to) -263.1000061035 (th) ] TJ
16.2933998108 0 TD
-0.0339000002 Tc
[(e) -257.8999938965 (vaccine) -257.8999938965 (demo) 3.9000000954 (nstrated) -258.200012207 (redu) ] TJ
10.8736000061 0 TD
-0.0361000001 Tc
[(ce) -5 (d) -260.5 (c) -1.6000000238 (og) -5.3000001907 (ni) -3.9000000954 (ti) -3.7999999523 (ve) -260.1000061035 (de) -5 (cli) -3.7999999523 (n) -4 (e,) -261.299987793 (su) -3.7000000477 (pp) -5.3000001907 (or) -5.9000000954 (tin) -4 (g) -260.3999938965 (th) -4 (e) -260.1000061035 (h) 1.7000000477 (yp) -5.3000001907 (o) -4 (t) -0.6000000238 (he) -5 (si) -3.9000000954 (s) -256 (t) -0.6000000238 (h) -4 (a) -3 (t) ] TJ
-27.1671009064 -1.1962000132 TD
0 Tc
(A) Tj
/F7 1 Tf
0.5442000031 0 TD
() Tj
/F5 1 Tf
0.782400012 0 TD
-0.0351999998 Tc
[(imm) -5.5999999046 (u) 2.9000000954 (n) -3.0999999046 (o) -3.0999999046 (t) 0.3000000119 (h) -3.0999999046 (e) 1.6000000238 (rap) -4.4000000954 (y) -267.200012207 (m) -5.5999999046 (a) 3.5999999046 (y) -272.799987793 (h) -3.0999999046 (ave) -270.5 (cli) -2.9000000954 (n) -3.0999999046 (ical) -2.9000000954 (ly) -272.799987793 (re) -4.0999999046 (le) -4.0999999046 (vant) -271.799987793 (e) 1.6000000238 (ffe) -4.0999999046 (cts.) -271.700012207 (Bapi) -2.9000000954 (n) -3.0999999046 (e) 1.6000000238 (u) -2.7999999523 (z) ] TJ
22.6940002441 0 TD
-0.0331000015 Tc
[(umab) -268.799987793 (\(Elan) 4.6999998093 (/) -1.8999999762 (Pfi) 4.8000001907 (z) -0.8999999762 (er) -269.299987793 (In) 4.6999998093 (c./Jo) 4.6999998093 (hnson) -267.3999938965 (&) -269.1000061035 (J) 3.7999999523 (oh) 4.6999998093 (nson) 4.6999998093 (\),) -269.6000061035 (a) -272.1000061035 (m) 2.2000000477 (on) 4.6999998093 (oclo) 4.6999998093 (nal) ] TJ
-24.0205993652 -1.2019000053 TD
-0.0361000001 Tc
[(anti) -3.7999999523 (bo) -4 (dy) -273.700012207 (tar) -5.9000000954 (g) 0.3000000119 (et) -6.1999998093 (in) -4 (g) -271.799987793 (f) -2.9000000954 (ib) -5.3000001907 (ri) -3.7999999523 (ll) -3.7999999523 (ar) -272.299987793 (A) ] TJ
/F7 1 Tf
10.3123998642 0 TD
0 Tc
() Tj
/F5 1 Tf
0.5045999885 0 TD
-0.0359999985 Tc
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16.2651004791 0 TD
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-27.0820007324 -1.2019000053 TD
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/F7 1 Tf
21.6396007538 0 TD
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() Tj
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-22.1497993469 -1.1962000132 TD
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15.913599968 0 TD
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-15.913599968 -1.2019000053 TD
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T*
-0.0344000012 Tc
[(soluble) -269.700012207 (A) ] TJ
/F7 1 Tf
3.429899931 0 TD
0 Tc
() Tj
/F5 1 Tf
0.7767000198 0 TD
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/F7 1 Tf
5.9924001694 0 TD
0 Tc
() Tj
/F5 1 Tf
0.782400012 0 TD
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17.2798995972 0 TD
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[(y) -272 (t) 1.1000000238 (o) -268.700012207 (b) -3.5999999046 (e) -269.700012207 (p) 2 (resent) -271 (in) -274.3999938965 (all) -268.6000061035 (c) -5.5999999046 (a) 4.4000000954 (s) -4.9000000954 (es) -271.299987793 (of) -267.6000061035 (AD.) -265.200012207 (A) -273.3999938965 (monoclonal) ] TJ
-28.2611999512 -1.1962000132 TD
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/F7 1 Tf
17.1494998932 0 TD
0 Tc
() Tj
/F5 1 Tf
0.7767000198 0 TD
-0.0335000008 Tc
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14.501999855 0 TD
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[(t) -270.8999938965 (l) -2 (east) -270.8999938965 (a) -267.6000061035 (1) -3.2000000477 (,00) -3.2000000477 (0) 2.5 (-) -4.0999999046 (f) 4.5999999046 (old) -270 (h) 3.5 (ighe) -3.2000000477 (r) -264.8999938965 (s) -4.8000001907 (electivit) -4.4000000954 (y) -266.299987793 (for) ] TJ
-32.4281005859 -1.2019000053 TD
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[(protofi) 4.0999999046 (b) -3 (ril) 4.0999999046 (s) -270.700012207 (as) -270.700012207 (co) 4 (mpared) -269.5 (wi) 4.0999999046 (th) -273.799987793 (mon) 4 (o) -1.7000000477 (mers) -270.700012207 (o) 4 (f) -272.700012207 (A) ] TJ
/F7 1 Tf
17.0077991486 0 TD
0 Tc
() Tj
/F5 1 Tf
0.5045999885 0 TD
-0.0335999988 Tc
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13.4984998703 0 TD
-0.0346000008 Tc
[(he) -269.8999938965 (pe) -3.5 (ptid) -3.7999999523 (e.) -271.1000061035 (A) -268 (h) -2.5 (umanized) -270.299987793 (ve) -3.5 (rsion) -274.6000061035 (o) 3.2000000477 (f) ] TJ
-31.010799408 -1.2019000053 TD
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[(mAb1) -4.1999998093 (58,) -271.799987793 (BAN2) -4.1999998093 (40) -4.1999998093 (1,) -271.799987793 (has) -272.200012207 (n) -3.2000000477 (ow) -275.3999938965 (enter) -5.0999999046 (e) 1.5 (d) -271 (a) -274.299987793 (clinical) -269.5 (p) -4.5 (h) -3.2000000477 (as) -5.8000001907 (e) -270.6000061035 (2) 1.5 (b) -271 (t) 0.200000003 (r) -5.0999999046 (i) 2.5999999046 (al) -269.5 (in) ] TJ
23.4934005737 0 TD
-0.0348000005 Tc
[(a) -273.799987793 (c) -0.3000000119 (ollaboration) -274.799987793 (bet) -4.9000000954 (w) 2.9000000954 (e) -3.7000000477 (e) 2 (n) -269.200012207 (B) -5.3000001907 (ioAr) ] TJ
11.2250995636 0 TD
-0.0337999985 Tc
[(ctic) -265.799987793 (Neuroscience) -269.1000061035 (and) -269.5 (E) -1 (isai) ] TJ
-34.71849823 -1.1962000132 TD
-0.0331000015 Tc
[(w) 4.5999999046 (i) -0.8000000119 (tho) 4.6999998093 (u) -0.6999999881 (t) -269.700012207 (t) 2.4000000954 (he) -268.3999938965 (safe) 3.7000000477 (ty) -270.700012207 (con) 4.6999998093 (c) 1.3999999762 (erns) -270 (se) 3.7000000477 (en) -267.3999938965 (i) 4.8000001907 (n) -273.1000061035 (p) 3.2999999523 (r) 2.7999999523 (evi) 4.8000001907 (o) -1 (us) -270 (p) 3.2999999523 (h) -1 (ase) -268.3999938965 (1) -268.3999938965 (a) 0 (n) 4.6999998093 (d) -268.799987793 (2a) -266.3999938965 (tria) ] TJ
23.9752998352 0 TD
-0.0342999995 Tc
[(ls.) -270.799987793 (E) -1.5 (xperiences) -271.200012207 (from) -271.1000061035 (the) -269.6000061035 (f) -1.1000000238 (ield) -270 (indicate) -269.6000061035 (the) -269.6000061035 (i) 3.5999999046 (mportance) -269.6000061035 (o) 3.5 (f) ] TJ
-23.9752998352 -1.2019000053 TD
-0.0364000015 Tc
[(in) -4.3000001907 (it) -6.5 (iati) -4.0999999046 (n) -4.3000001907 (g) -272.1000061035 (tre) -5.3000001907 (a) 2.4000000954 (t) -6.5 (m) -1.1000000238 (en) -4.3000001907 (t) -273 (e) 0.400000006 (arl) -4.0999999046 (y) -274 (in) -276.3999938965 (the) -271.700012207 (c) -1.8999999762 (o) -4.3000001907 (u) -4 (rse) -271.700012207 (o) -4.3000001907 (f) -269.6000061035 (t) -6.5 (he) -271.700012207 (d) -5.5999999046 (i) 1.5 (s) -6.9000000954 (e) 0.400000006 (ase) -271.700012207 (a) -3.2999999523 (n) -4.3000001907 (d) -272.1000061035 (of) ] TJ
22.4503002167 0 TD
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[(enrich) 4.0999999046 (ing) -269.3999938965 (t) 1.7999999523 (h) 4.0999999046 (e) -274.700012207 (trial) -267.8999938965 (p) 2.7000000477 (opulati) 4.1999998093 (o) -1.6000000238 (n) -268 (b) -2.9000000954 (y) -265.700012207 (i) -1.3999999762 (mprovi) 4.1999998093 (ng) -269.3999938965 (the) -269 (d) 2.7000000477 (iagno) 4.0999999046 (s) -4.1999998093 (ti) 4.1999998093 (c) ] TJ
-22.4503002167 -1.2019000053 TD
-0.0344999991 Tc
[(accuracy.) -271 (BAN2401) -269.799987793 (i) -2.2000000477 (s) -265.799987793 (a) -273.5 (pr) ] TJ
9.4677000046 0 TD
-0.0328000002 Tc
[(o) 5 (m) -3.2000000477 (i) 5.0999999046 (s) 2.4000000954 (ing) -268.5 (c) 1.7000000477 (an) 5 (di) 5.0999999046 (date) -268.1000061035 (fo) 5 (r) -269 (A) ] TJ
/F7 1 Tf
8.9176998138 0 TD
0 Tc
() Tj
/F5 1 Tf
0.7767000198 0 TD
-0.0342999995 Tc
[(immunotherapy) -271.8999938965 (i) -2 (n) -268.700012207 (e) 2.5 (arly) -271.8999938965 (AD) 4.0999999046 (.) -270.799987793 (O) -3.2999999523 (ther) -270.5 (en) ] TJ
14.0426998138 0 TD
[(couraging) -275.6000061035 (e) 2.5999999046 (fforts) -265.5 (i) ] TJ
6.7010998726 0 TD
-0.0344000012 Tc
[(n) -268.700012207 (i) -2.2000000477 (mmunot) -4.5 (h) 3.4000000954 (erapy) ] TJ
-39.9058990479 -1.1962000132 TD
-0.0331000015 Tc
[(as) -264.3999938965 (wel) 4.8000001907 (l) -267.299987793 (as) -270 (in) -267.5 (the) -268.3999938965 (s) 2.0999999046 (mall) 4.8000001907 (-mol) 4.8000001907 (ecu) 5 (l) -0.8999999762 (e) -268.3999938965 (f) 0.1000000015 (ield) -268.799987793 (o) 4.6999998093 (ffer) -269.299987793 (h) -1 (o) 4.6999998093 (p) -2.2999999523 (e) -268.3999938965 (f) ] TJ
18.1415996552 0 TD
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[(o) 5.0999999046 (r) -268.8999938965 (new) -272.799987793 (i) 5.1999998093 (nno) 5.0999999046 (vative) -268 (t) 2.7999999523 (herapi) 5.1999998093 (es) -264 (for) -268.8999938965 (A) 0.400000006 (D) -266.3999938965 (i) -0.400000006 (n) -267.1000061035 (t) 2.7999999523 (he) -268 (fu) 5.4000000954 (tu) 5.4000000954 (re.) ] TJ
/F1 1 Tf
10.3000001907 0 0 10.3000001907 56.6929016113 221.7259979248 Tm
0 Tc
[(Introduc) -10.8000001907 (tion) ] TJ
/F8 1 Tf
9.7999000549 0 0 9.7999000549 56.6929016113 209.7637939453 Tm
[(Immun) -8.8000001907 (otherap) -10.3999996185 (y) -432.299987793 (h) 0 (a) -12.8000001907 (s) -430.700012207 (eme) -8.5 (rged) -435.700012207 (a) -10 (s) -430.700012207 (a) -432.299987793 (prom) -8.6999998093 (ising) -435.8999938965 (treatment) ] TJ
0 -1.2264000177 TD
[(option) -401.6000061035 (for) -404.8999938965 (Alzheimer) ] TJ
/F9 1 Tf
9.0361995697 0 TD
<92> Tj
/F8 1 Tf
0.133100003 0 TD
[(s) -401.799987793 (disea) -12.6000003815 (se) -400.200012207 (\(AD\),) -402.6000061035 (the) -402.3999938965 (most) -404.3999938965 (common) ] TJ
-9.1693000793 -1.2264000177 TD
[(form) -358.700012207 (of) -351.799987793 (deme) -9.8000001907 (ntia) -357 ([1].) -354.200012207 (The) -347.6000061035 (lack) -359.200012207 (of) -351.799987793 (an) -354.700012207 (effe) -16.6000003815 (ctive) -362.700012207 (treatment) ] TJ
0 -1.220600009 TD
[(is) -488.8999938965 (an) -487.799987793 (increa) -17.3999996185 (sing) -487.6000061035 (socioe) -18.5 (cono) -8.8999996185 (mic) -484.799987793 (thre) -10 (at.) -488.200012207 (Although) -496.200012207 (many) ] TJ
0 -1.2264000177 TD
[(challe) -10.3999996185 (nges) -404.799987793 (rema) -9.6000003815 (in,) -404.700012207 (data) -410.799987793 (from) -410.700012207 (drug) -405.3999938965 (progra) -9.3000001907 (ms) -407.6000061035 (within) -411 (the) ] TJ
T*
[(immunoth) -12 (erapy) -431.5 (area) -430.299987793 (indicat) -9.8999996185 (e) -426.5 (that) -427.5 (treatme) -11.8999996185 (nt) -427.6000061035 (effe) -16.5 (ct) -12 (s) -424.8999938965 (are) ] TJ
25.3094997406 7.3470001221 TD
[(possible) -12.6000003815 (,) -337.3999938965 (providing) -343.8999938965 (hope) -344.5 (for) -341.299987793 (a) -339.799987793 (new) -346.1000061035 (generation) -348.6000061035 (of) -340.200012207 (therap) -9.6999998093 (-) ] TJ
0 -1.220600009 TD
[(ies) -302.200012207 (in) -304.5 (the) -304 (future.) ] TJ
0.8156999946 -1.2264000177 TD
[(The) -428.6000061035 (underlying) -438.6000061035 (patho) -10.8999996185 (genic) -435.6000061035 (me) -15.8999996185 (chanism) -439.8999938965 (for) -433.799987793 (the) -431.299987793 (de) -17 (vel-) ] TJ
-0.8156999946 -1.2264000177 TD
[(opmen) -9.5 (t) -291.200012207 (o) 0 (f) -293.8999938965 (A) 0 (D) -292.700012207 (i) 0 (s) -292.200012207 (subje) -14.8000001907 (ct) -295.3999938965 (to) -297.700012207 (ongoing) -294.200012207 (di) -7.3000001907 (scussions.) -301.299987793 (Accord-) ] TJ
0 -1.220600009 TD
[(ing) -554.4000244141 (to) -558 (the) -564.4000244141 (amyloid) -560.700012207 (hypo) -8.8999996185 (thesis) -26.1000003815 (,) -557.200012207 (the) -558.5999755859 (amylo) -9.5 (id-beta) -562.700012207 (\(A) ] TJ
/F10 1 Tf
23.0359992981 0 TD
() Tj
/F8 1 Tf
0.5033000112 0 TD
(\)) Tj
-23.5393009186 -1.2264000177 TD
[(pepti) -9 (de,) -481.700012207 (whic) -10.3999996185 (h) -483 (i) 0 (s) -483.1000061035 (the) -489.200012207 (main) -488.1000061035 (constitu) -12.1000003815 (ent) -483.8999938965 (of) -484.8999938965 (ext) -8.8999996185 (racellular) ] TJ
T*
-0.0001 Tc
[(plaques) -583.700012207 (found) -584.9000244141 (in) -576.5 (AD) -576.299987793 (brains) -585 ([2],) -579.9000244141 (initia) -10.6999998093 (tes) -575.799987793 (the) -581.799987793 (disea) -18.5 (se) ] TJ
0 -1.220600009 TD
0 Tc
[(process) -323.200012207 (an) -7.5999999046 (d) -313.6000061035 (the) -9 (refore) -321.799987793 (is) -321.1000061035 (an) -320 (attractive) -329.799987793 (target) -321.200012207 (for) -323.8999938965 (inter) -34.0999984741 (ven-) ] TJ
0 -1.2264000177 TD
[(tion) -509.6000061035 ([3,4].) -510.3999938965 (This) -496.700012207 (hyp) -8.3000001907 (othesis) -512.700012207 (ha) -12.8000001907 (s) -505.8999938965 (been) -510 (supp) -7.9000000954 (orted) -512.4000244141 (by) -508.200012207 (the) ] TJ
T*
[(finding) -8 (s) -505.8999938965 (o) 0 (f) -513.799987793 (s) 0 (e) -12.6000003815 (veral) -512.200012207 (muta) -9.1000003815 (tions) -512.200012207 (in) -507 (the) -512.299987793 (A) ] TJ
/F10 1 Tf
17.048500061 0 TD
() Tj
/F8 1 Tf
1.0297000408 0 TD
[(region) -514.0999755859 (of) -513.799987793 (the) ] TJ
-18.0781993866 -1.220600009 TD
[(amyl) -8.8999996185 (oid-beta) -615.4000244141 (pre) -12.3000001907 (cursor) -614 (protein) -614.5 (\(A) ] TJ
/F10 1 Tf
15.2955999374 0 TD
() Tj
/F8 1 Tf
0.5206000209 0 TD
[(PP\)) -613.5 (a) -10 (s) -604.200012207 (well) -609.5 (a) -15.8000001907 (s) -604.200012207 (in) ] TJ
ET
q
56.6930007935 138.1040039062 m
290.550994873 138.1040039062 l
290.550994873 93.9400024414 l
56.6930007935 93.9400024414 l
W
n
0 0 0 1 K
0.112999998 w
q
1 0 0 1 56.6930007935 138.0469970703 cm
0 0 m
233.858001709 0 l
S
Q
Q
BT
/F5 1 Tf
7.4998998642 0 0 7.4998998642 56.6929016113 129.9402008057 Tm
0 0 0 rg
[(*) -265.1000061035 (Correspon) -13.8000001907 (dence:) ] TJ
0 0 0 1 k
7.7178997993 0 TD
[(Lars.Lannf) -14.8000001907 (elt@pubcare.uu.se) ] TJ
5.6248002052 0 0 4.9991998672 56.6929016113 124.2707977295 Tm
0 0 0 rg
(1) Tj
7.4998998642 0 0 7.4998998642 59.3574981689 120.9826965332 Tm
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