ライフサイエンスコーパス: Abeta40

1 Abeta40 aggregated into amyloid fibrils, whereas Abeta42

2 Abeta40 levels increased by 63% (p < 0.001) in the corte

3 Abeta40 was retrospectively measured in blood samples co

4 Abeta40, by contrast, does not significantly form the he

5 Abeta40/tau ratio was associated with Brief Visuospatial

6 e baseline (HMW vs. LMW) was 36.9 vs. 74.1% (Abeta40, P<0.05) and 25.4 vs. 88.0% (Abeta42, P<0.01)],

7 -fibrillar morphology, the metastable Zn(2+)-Abeta40 oligomers are rich in beta-sheet and cross-beta

8 ow that small Zn(2+)-bound Abeta1-40 (Zn(2+)-Abeta40) oligomers formed in cell culture medium exhibit

9 mational ensembles of the amyloid-beta 1-40 (Abeta40) and amyloid-beta 1-42 (Abeta42) peptides genera

10 ine the clinical value of amyloid-beta 1-40 (Abeta40) measurement in predicting cardiovascular (CV) m

11 F samples were analyzed for beta-amyloid 40 (Abeta40), Abeta42, total tau, tau phosphorylated at thre

12 steady-state level and less amyloid-beta-40 (Abeta40) peptide uptake.

13 , BACE1, and the two primary forms of Abeta (Abeta40 and Abeta42) in a primary human cell culture mod

14 howed a single predominant 40 residue Abeta (Abeta40) fibril structure in each patient; however, the

15 he structural evolution of 40-residue Abeta (Abeta40) is monitored by ssNMR measurements on frozen so

16 ecretase produces multiple species of Abeta: Abeta40, short Abeta peptides (Abeta37-39), and longer A

17 LF/LF) rats exhibited low levels of Abeta38, Abeta40, and Abeta42 peptides.

18 and beta (sAPPbeta), Abeta species (Abeta38, Abeta40 and Abeta42), total tau (T-tau), phosphorylated

19 otal amount of Abeta (Abeta-Total), Abeta38, Abeta40, and Abeta42 were achieved both in cell culture

20 ted rat brain capillaries to 100 nm Abeta40, Abeta40, aggregated Abeta40, and Abeta42.

21 ons and consisted of a reduction in Abeta42, Abeta40, and Abeta38 and in the Abeta42:Abeta40 ratio, w

22 VLP-1, and HFABP), APP metabolism (Abeta42, Abeta40, Abeta38, sAPPalpha, and sAPPbeta), tangle patho

23 cterize the structural ensembles of Abeta42, Abeta40, and M35-oxidized Abeta42, three physiologically

24 conspiring to increase the critical Abeta42/Abeta40 ratio implicated in AD pathogenesis.

25 The high Abeta42/Abeta40 production ratio is a hallmark of familial Alzhe

26 suggested by a significantly reduced Abeta42/Abeta40 ratio in the hippocampus, improved basal synapti

27 n parenchyma, and an increase in the Abeta42/Abeta40 ratio is correlated with early-onset AD.

28 d reduced in KI/+ brains, though the Abeta42/Abeta40 ratio is slightly increased in KI/+ brains.

29 soluble Abeta40 and Abeta42, and the Abeta42/Abeta40 ratio were reduced in APP/PS1/tau(-/-) mice.

30 f Abeta40 and Abeta42, increased the Abeta42/Abeta40 ratio, and exacerbated Abeta deposition.

31 duced by proteolysis, as well as the Abeta42/Abeta40 ratio, both of which are linked to the progressi

32 e Abeta40 formation and increase the Abeta42/Abeta40 ratio.

33 secretase leads to the gain of toxic Abeta42/Abeta40.

34 oncordance of CSF Abeta42 levels and Abeta42:Abeta40 and Abeta42:tau ratios with visual [18F]flutemet

35 the benefit of implementing the CSF Abeta42:Abeta40 or Abeta42:tau ratios as a biomarker of amyloid

36 au181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures (AUC range, 0.67-0.90; P

37 nt PS1 neurons exhibited an elevated Abeta42:Abeta40 ratio (P < .05) at the basal state as compared w

38 intriguing in light of the increased Abeta42:Abeta40 ratios shown to correlate with familial Alzheime

39 and grow at rates dependent on local Abeta42:Abeta40 ratios.

40 etamol PET assessment when using the Abeta42:Abeta40 or Abeta42:tau ratios.

41 , plaques were more diffuse, and the Abeta42:Abeta40 ratio and amount of soluble, fibrillar Abeta oli

42 A combination of the Abeta42:Abeta40 ratio and T-tau or P-tau level did not improve t

43 in PS2APP;Trem2(ko) brains, and the Abeta42:Abeta40 ratio was elevated.

44 a42, Abeta40, and Abeta38 and in the Abeta42:Abeta40 ratio, with no change in the total Abeta levels.

45 r assays improved significantly when Abeta42:Abeta40 (AUCs, 0.93-0.95; P </= .01), Abeta42 to total t

46 hat physiological ionic strength accelerates Abeta40 aggregation kinetics by promoting surface-cataly

47 d this interaction decreased BACE1 activity, Abeta40 and 42 levels.

48 After multivariate adjustment, Abeta40 levels conferred a substantial enhancement of ne

49 aries to 100 nm Abeta40, Abeta40, aggregated Abeta40, and Abeta42.

50 simulations, we show that freely aggregating Abeta40 oligomers in physiological solutions have an int

51 Plaques were also Abeta40-, Abeta42-, and Abeta oligomer-immunoreactive, b

52 No differences in extracellular amylin, Abeta40, or Abeta42 were detected, yet only supernatant

53 sult in decrease of release of amyloidogenic Abeta40 fragments.

54 in the levels of amyloid beta (Abeta)42 and Abeta40.

55 ent to drive Abeta42 deposition, Abeta38 and Abeta40 did not deposit or cause behavioral alterations.

56 ted virus-mediated expression of Abeta38 and Abeta40 in mice.

57 CSF Abeta38 and Abeta40 were associated with regional WML in all regions

58 Lower CSF levels of Abeta38 and Abeta40 were consistently associated with increased WML

59 f Abeta species, particularly of Abeta38 and Abeta40.

60 protein (APP) and extracellular Abeta42 and Abeta40 (the 42- and 40-residue isoforms of the amyloid-

61 Lipid-depleted Abeta42 and Abeta40 and apolipoprotein E in cerebrospinal fluid.

62 ze interpeptide interactions for Abeta42 and Abeta40 and corresponding mutants.

63 Abeta42 and Abeta40 are the two primary alloforms of human amyloid b

64 Abeta42 and Abeta40 differ only near the C-terminus, where curcumin

65 ls compared with the predominant Abeta42 and Abeta40 forms, but it has been suggested that this longe

66 We analyzed plasma levels of Abeta42 and Abeta40 in a cohort of 719 individuals (the Swedish BioF

67 e modulatory profile by lowering Abeta42 and Abeta40 levels combined with an especially pronounced in

68 in APP-CTFalpha and decrease in Abeta42 and Abeta40 levels.

69 e in the interaction patterns of Abeta42 and Abeta40 monomers within dimers.

70 -associated virus (AAV) encoding Abeta42 and Abeta40 peptides fused to BRI2 protein by intraocular in

71 increases the ratio between the Abeta42 and Abeta40 peptides largely due to a decrease in Abeta40 fo

72 leads to production of secreted Abeta42 and Abeta40 respectively.

73 heimer's disease, whereas plasma Abeta42 and Abeta40 were not.

74 Plasma levels of Abeta42 and Abeta40 were reduced in AD dementia compared with all ot

75 inal fluid (CSF) levels for both Abeta42 and Abeta40, and negative correlations between plasma Abeta4

76 ficant increase in extracellular Abeta42 and Abeta40.

77 ne (PolyQ) proteins, firefly luciferase, and Abeta40.

78 r the same fibrillization conditions, Arctic Abeta40 exhibits a high degree of polymorphism, showing

79 orms of Abeta peptide associated with AD are Abeta40 and Abeta42, of which the latter is highly prone

80 taE9 reduces amyloid plaque load, as well as Abeta40 and Abeta42 levels in hippocampus of 9-month-old

81 inked immunosorbent assay was used to assess Abeta40 levels in brain and plasma after oral administra

82 ically disordered, polypeptide amyloid beta (Abeta40) bound to GroEL.

83 at there is a qualitative difference between Abeta40 and Abeta42 aggregates in the brain tissue of pa

84 peptide to identify the differences between Abeta40 and Abeta42 in terms of the microscopic determin

85 ons produced amyloid plaques containing both Abeta40 and Abeta42 in the brains of inoculated bigenic

86 Sites causing substantial effects in both Abeta40 and Abeta42 include His14, Gln15, Ala30, Ile31,

87 ed with aging followed by a decrease of both Abeta40 and Abeta42 upon CAA onset, supporting the idea

88 vage of APP and increased production of both Abeta40 and Abeta42.

89 d age diminished day/night amplitude of both Abeta40 and Abeta42.

90 cursor protein, pericyte loss elevates brain Abeta40 and Abeta42 levels and accelerates amyloid angio

91 LRPIV-D3674G cleared mouse endogenous brain Abeta40 and Abeta42 25-27% better than WT-LRPIV.

92 As in the brain, Abeta40 and Abeta42 are present in the heart, and their

93 iguingly, simultaneous overexpression of BRI-Abeta40 or BRI-Abeta42 together resulted in dose-depende

94 in (APP) metabolites (secreted APPbeta, C99, Abeta40, and Abeta42) but has no effect on presenilin 1

95 a resulted in a significant reduction of CNS Abeta40 in naive rats.

96 the optimized detergent micelle conditions, Abeta40 and Abeta42 showed different behavior.

97 Bi-4), which robustly lowered CSF and cortex Abeta40 in both rats and cynomolgus monkeys following a

98 and for a combination of CSF Abeta38 and CSF Abeta40.

99 The association between CSF Abeta40 and brain Abeta is stronger in APOE varepsilon4-

100 ) are independently associated with high CSF Abeta40 (P<0.001) and APOE varepsilon4 (P<0.001).

101 Despite comparably low CSF Abeta40 and Abeta42, PiB retention was substantially les

102 ting the idea that combined reduction of CSF Abeta40 and Abeta42 is a specific biomarker for vascular

103 on in D-CAA and correlation with reduced CSF Abeta40 suggest this compound labels vascular amyloid, a

104 ibitor, was able to reduce significantly CSF Abeta40 and 42 in rats at oral doses as low as 1 mg/kg.

105 INDER study, using cerebrospinal fluid (CSF) Abeta40 as a surrogate for amyloidogenic APP processing.

106 ural changes in the T43I mutant may decrease Abeta40 formation and increase the Abeta42/Abeta40 ratio

107 llagen binding to GPVI resulted in decreased Abeta40-stimulated platelet activation, factor secretion

108 d that the T43I/A21G double mutant decreases Abeta40 formation.

109 cture-assembly relationships of 76 different Abeta40 and Abeta42 peptides.

110 patients suffering from Alzheimer's disease, Abeta40 and Abeta42, only differ by two amino acids in t

111 d compared with wild-type and Osaka E22Delta Abeta40 fibrils.

112 ics, hydration and morphology of Arctic E22G Abeta40 fibrils.

113 polymorphism is intrinsic to the Arctic E22G Abeta40 sequence.

114 (13)C, (15)N-labeled synthetic E22G Abeta40 peptides are studied and compared with wild-type

115 When assembling as fibrils Abeta40 peptides can only assume U-shaped conformations

116 Cerebrospinal fluid Abeta40 was reduced at 6 months and Abeta42 was reduced

117 ming a marginally stable, short-lived folded Abeta40 species.

118 Our findings suggest that the folded Abeta40-Zn(2+) complex modulates the fibril ends, where

119 .6- and 2.7-fold higher binding affinity for Abeta40 and Abeta42 in vitro, respectively, and a lower

120 e salt decreases the free-energy barrier for Abeta40 folding to the Fbeta state, favoring the buildup

121 e of a minimal antiaggregation chaperone for Abeta40.

122 Here it is shown that the data for Abeta40 and Abeta42 require that the nuclei be monomeric

123 A molecular structural model developed for Abeta40 fibrils from one patient reveals features that d

124 approach to the comparison of ensembles for Abeta40 and Abeta42.

125 ryonic kidney 293 cell lines were tested for Abeta40 and Abeta42 secretion, and the amount of the amy

126 of Abeta42 peptide is smaller than that for Abeta40.

127 a42 fibrils that were indistinguishable from Abeta40 fibrils produced in the absence or presence of S

128 ajor tripeptide-cleaving pathways generating Abeta40 and Abeta42 at several points, implying that the

129 f Abeta: Abeta49 --> Abeta46 --> Abeta43 --> Abeta40 and Abeta48 --> Abeta45 --> Abeta42 --> Abeta38.

130 Tg-SwDI mice for 8 weeks resulted in higher Abeta40 levels and increased thioflavin S-positive fibri

131 Changes in Abeta40, Abeta42, total tau, P-tau181, VILIP-1, and YKL-

132 GSMs caused a decrease in Abeta40 and Abeta42 and an increase in Abeta37 and Abeta

133 ulators (GSMs) cause a selective decrease in Abeta40 and Abeta42 and an increase in shorter Abeta pep

134 concentration and time dependent decrease in Abeta40 and Abeta42 levels in plasma, brain, and CSF was

135 beta40 peptides largely due to a decrease in Abeta40 formation.

136 a42, the absence of a second beta-hairpin in Abeta40 and the sampling of alternate beta topologies by

137 were no consistent longitudinal patterns in Abeta40 (P = .001-.97), longitudinal reductions in Abeta

138 al36-Gly37 in Abeta42 that is not present in Abeta40.

139 ssing, which in turn can result in increased Abeta40 and Abeta42 secretion.

140 Transfected cell lines showed increased Abeta40 and Abeta42 secretion for the rare variants (E27

141 (APDeltaE9/COPS5-Tg) significantly increased Abeta40 levels by 32% (p < 0.01) in the cortex and by 28

142 Remarkably, tranilast increases Abeta40 fibrillation more than 20-fold in the thioflavin

143 The levels of soluble and insoluble Abeta40 and Abeta42, and the Abeta42/Abeta40 ratio were

144 ralleled by an increase of the intermediates Abeta40-38 and Abeta42-39.

145 When substituted into Abeta40, the VPV substitution caused the peptide to olig

146 the increases in secreted and intracellular Abeta40 were abolished by depletion of presenilin 2 (PSE

147 umulation of both secreted and intracellular Abeta40.

148 d the aggregation of its two major isoforms, Abeta40 and Abeta42, using a statistical mechanical mode

149 sed these fractions (LD Abeta42, P = .01; LD Abeta40, P = .15).

150 Abeta42 and insulin, r = -0.68 [P = .01]; LD Abeta40 and insulin, r = -0.78 [P = .002]).

151 th normal cognition (LD Abeta42, P = .05; LD Abeta40, P = .01).

152 g positively and negatively charged ligands, Abeta40-cut-peptide, and synthetic inhibitor ligands, in

153 , we show that FXIIIa covalently cross-links Abeta40 into dimers and oligomers (k (cat)/K(m) = 1.5 x

154 ning the salt bridge to emerge in the mature Abeta40 aggregates, but not in Abeta42.

155 The modified Abeta40 was significantly more toxic than Abeta40.

156 t to bind various conformations of monomeric Abeta40 and alpha-synuclein to form structurally diverse

157 sed isolated rat brain capillaries to 100 nm Abeta40, Abeta40, aggregated Abeta40, and Abeta42.

158 hanced neuronal binding for E22Delta but not Abeta40 with subsequent intraneuronal accumulation in ly

159 rhMMP-2, although the enzyme cleaved >80% of Abeta40 during the 1st h of incubation.

160 ed a comprehensive analysis of the amount of Abeta40 and Abeta42 in increasingly insoluble fractions,

161 rolling for amyloid deposition, amplitude of Abeta40 was positively associated with production rates

162 Binding of Abeta40 to integrin alpha(IIb)beta(3), fibrinogen, and G

163 creting the factor clusterin upon binding of Abeta40 to the fibrinogen receptor integrin alpha(IIb)be

164 he major source of aggregates in the case of Abeta40 is a fibril-catalyzed nucleation process, the mu

165 ssociated with reduced CSF concentrations of Abeta40 (r = -0.55, p = 0.021) but not Abeta42 (r = 0.01

166 more complex than age-related conversion of Abeta40 and alpha-synuclein into single amyloid-prone co

167 Dose-dependent decrease of Abeta40 levels in vivo confirmed suppression of BACE1 ac

168 evels and activity impact the degradation of Abeta40 and Abeta42 into a common Abeta34 intermediate.

169 cortex consistent with earlier deposition of Abeta40-42 in the hippocampus and ibuprofen protects aga

170 to present monomeric structural ensembles of Abeta40 and Abeta42 consistent with available informatio

171 of gamma-secretase leads to the formation of Abeta40 and Abeta42 whether the protease complex is dete

172 We show that all methyl groups of Abeta40 populate direct-contact bound states with a very

173 beled leucine was performed, and kinetics of Abeta40 and Abeta42 were measured.

174 Production and steady-state levels of Abeta40 and Abeta42 are undetectable in KI/KI brains and

175 variant had, on average, 28% lower levels of Abeta40 and Abeta42 in plasma as compared to the control

176 In addition, we observed increased levels of Abeta40 and Abeta42 peptides in the lipid-associated fra

177 CD81-normalized EDE levels of Abeta40 and Abeta42 were significantly higher in the pAD

178 Measuring blood levels of Abeta40 identified patients at high risk for CV death.

179 Baseline levels of Abeta40 in the ISF are relatively stable and begin to de

180 High EDE levels of Abeta40, Abeta42, and phospho-181T-tau in patients with

181 ically disordered protein (SOP-IDP) model of Abeta40 and Abeta42.

182 to Fbeta, underlining the dynamic nature of Abeta40 fibrils in solution.

183 de and linear increase of Abeta42 but not of Abeta40.

184 for the KI mutation decreased production of Abeta40 and Abeta42, increased the Abeta42/Abeta40 ratio

185 -type PS1 while decreasing its production of Abeta40.

186 eta, resulted in significant prolongation of Abeta40 half-life, but only in the latter phase of Abeta

187 lasting, showing a significant reduction of Abeta40 and 42 even after 24 h.

188 etase leads to the production and release of Abeta40 and 42.

189 on of the two adjacent histidine residues of Abeta40 (H13,14G) resulted in a significant decrease in

190 ide NPs couple to the beta sheet surfaces of Abeta40 fibrils and only the negative-neutral NPs couple

191 ligomer size distribution similar to that of Abeta40.

192 that is about 10 times smaller than that of Abeta40.

193 primary endpoint was the predictive value of Abeta40 for CV mortality and outcomes in patients with C

194 nd no difference in the effects of Zn(+2) on Abeta40 and Abeta42.

195 easure the effects of Zn(2+) and curcumin on Abeta40, and compare these with their previously reporte

196 r magnetic resonance (ssNMR) measurements on Abeta40 and Abeta42 fibrils prepared by seeded growth fr

197 We observed that only Abeta40 triggered reduction of P-gp protein expression a

198 The simulations reveal that only Abeta40-cut-peptide-covered NPs have strong and selectiv

199 Shorter peptides (Abeta38 or Abeta40) and other longer peptides (nontoxic Abeta42 G33

200 ociation between preoperative CSF Abeta42 or Abeta40 to tau ratio and POCC.

201 lting in subsequent production of Abeta42 or Abeta40, respectively.

202 tion between preoperative CSF Abeta42/tau or Abeta40/tau ratio and the outcome measures described ear

203 The Osaka Abeta40 mutant shows lower hydration and more immobilize

204 c aggregation rates of amyloid beta peptide (Abeta40) self-association, implicated in Alzheimer's dis

205 ressing the 40-residue amyloid-beta peptide, Abeta40, wild-type and 24 charge mutants.

206 for the two major alloforms of the peptide, Abeta40 and the more toxic Abeta42.

207 by 40- and 42-residue amyloid-beta peptides (Abeta40 and Abeta42) are polymorphic, with variations in

208 the 40 and 42 residue amyloid-beta peptides (Abeta40 and Abeta42) have been implicated in the neurona

209 rate the existence of a specific predominant Abeta40 fibril structure in t-AD and PCA-AD, suggest tha

210 otein 1 (CNTNAP1), reduced Abeta production (Abeta40 and Abeta42) by around 70%, whereas knockdown of

211 Thus, Zn(2+) promotes Abeta40 neurotoxicity by structural organization mechani

212 d formation for the disease-related proteins Abeta40 and alpha-synuclein.

213 similar to those found in mice that received Abeta40 prions.

214 actions at the BBB and in the brain reduced Abeta40 and Abeta42 levels in brain markedly and normali

215 ce with LRPIV-D3674G (40 mug/kg/day) reduced Abeta40 and Alphabeta42 levels in the hippocampus, corte

216 rapalog-mediated proximity inducers reduced Abeta40 generation.

217 t assay (mean difference of SD of residuals: Abeta40, -7.42 pM; P < .001; Abeta42, -3.72 pM; P < .001

218 on was previously found to increase secreted Abeta40 levels; here, we combined this mutation in the e

219 demonstrate that overexpression of secreted Abeta40 or Abeta42 resulted in dramatic induction of dru

220 model for the interaction between 3Q-seeded Abeta40 fibrils and a major non-protein component of AD

221 nvestigate the water interactions of several Abeta40 fibrils.

222 s from 18 individuals, we find that a single Abeta40 fibril structure is most abundant in samples fro

223 ibing the structural transition of the small Abeta40 oligomers to fibrils.

224 d virus reduced the levels of BACE1, soluble Abeta40/42, amyloid plaque density, and rescued cognitiv

225 loidosis by diminishing clearance of soluble Abeta40 and Abeta42 from brain interstitial fluid prior

226 Levels of soluble Abeta40, Abeta42, tau, P-181 tau, and APOE genotype were

227 rt that, although bexarotene reduces soluble Abeta40 levels in one of the mouse models, the drug has

228 P/PS1 mice reduced CD33 mRNA and TBS-soluble Abeta40 and Abeta42 levels in brain extracts.

229 With 1 nM peptide in solution, Abeta40 oligomers do not grow over the course of 48 h, A

230 ation groups (P = .04) in contrast to stable Abeta40, tau, and total protein levels.

231 1 &Ala 42) that the non-pathological strain (Abeta40) lacks.

232 Synthetic Abeta40 preparations consisted of long straight fibrils;

233 er intracerebral inoculation, both synthetic Abeta40 and Abeta42 prions produced a sustained rise in

234 logical investigations showed that synthetic Abeta40 prions produced amyloid plaques containing both

235 ve protein, and high-sensitivity troponin T, Abeta40 independently predicted CV death and MACE in pat

236 The combination of the CSF biomarkers T-tau, Abeta40 and MCP-1 separates iNPH from cognitive and move

237 T-tau, Abeta40 and MCP-1 together yielded an area under the cur

238 A prediction algorithm consisting of T-tau, Abeta40 and MCP-1 was designed as a diagnostic tool usin

239 EPR spectra of tethered Abeta40 with spin labels at 18 different positions show

240 ic (3Q) morphology with higher affinity than Abeta40 fibrils in alternative structures, Abeta42 fibri

241 tate Abeta42 transport more efficiently than Abeta40, consistent with Abeta40 being the primary speci

242 2, which is only two amino acids longer than Abeta40, is particularly pathogenic.

243 2 exhibits greater fibrillization rates than Abeta40.

244 ed Abeta40 was significantly more toxic than Abeta40.

245 We demonstrate that Abeta40 drives P-gp ubiquitination, internalization, and

246 ficient human donors and mice, we found that Abeta40 bound to GPVI, which induced the release of ATP

247 Our findings indicate that Abeta40 promotes platelet-mediated amyloid aggregation b

248 the two additional C-terminal residues that Abeta40 lacks.

249 Further cohort-based analysis revealed that Abeta40 levels were significantly and independently asso

250 n labels at 18 different positions show that Abeta40 monomers adopt a completely disordered structure

251 ly, PSEN2 complexes discriminate between the Abeta40 and Abeta38 production lines, indicating that Ab

252 in the beta-strand content found between the Abeta40 and Abeta42 structural ensembles.

253 ramer form and the fibrillar pentamer in the Abeta40 aggregation landscape disappears for Abeta42, su

254 D23-K28 salt-bridge, a major feature of the Abeta40 fibrils and a focal point of mutations linked to

255 chemical kinetics to the aggregation of the Abeta40 peptide to identify the differences between Abet

256 xtend here this formalism to the case of the Abeta40 peptide, a 40-residue intrinsically disordered p

257 n, dramatically change the properties of the Abeta40 pool with A2V accelerating and A2T delaying aggr

258 b in complex with Abeta40 and found that the Abeta40 carboxyl moiety makes extensive contacts with po

259 f Abeta peptides and an increased Abeta38 to Abeta40 and Abeta42 ratio.

260 mechanisms by which the ratio of Abeta42 to Abeta40 can affect cell toxicity.

261 icles, and the ratios of products Abeta42 to Abeta40 follow a pattern consistent with the dual-pathwa

262 An increased ratio of Abeta42 to Abeta40 raises the fraction of oligomers containing Abet

263 r explore the nature of ponezumab binding to Abeta40, we determined the X-ray crystal structure of po

264 low-molecular-weight heparin (LMWH) binds to Abeta40 fibrils with a three-fold-symmetric (3Q) morphol

265 ion NMR to determine that tranilast binds to Abeta40 monomers with approximately 300 muM affinity.

266 Thus, exposing brain capillaries to Abeta40 triggers ubiquitination, internalization, and pr

267 nced aggregation rate of Abeta42 compared to Abeta40 be rationalized from the sparsely populated high

268 n residues of the Abeta42 strain compared to Abeta40.

269 ed NPs have strong and selective coupling to Abeta40 monomers.

270 itor ligands, in their selective coupling to Abeta40 peptides and their fibrils.

271 Altered trimming of long Abeta peptides to Abeta40 and Abeta42 by mutant proteases occurs at multip

272 vage significantly reduces APP processing to Abeta40.

273 ligomeric structures for Abeta42 relative to Abeta40, and greatly facilitate the conversion from pre-

274 Because Abeta42, relative to Abeta40, has a more prominent role in AD, the higher pro

275 ster aggregation rate of Abeta42 relative to Abeta40.

276 ncrease in the amount of Abeta42 relative to Abeta40.

277 Similar to Abeta40 and Abeta42, production of Abeta43 is undetectab

278 Sites whose effects were unique to Abeta40 include Lys16, Leu17, and Asn 27, whereas sites

279 te to the known dependency of the Abeta42-to-Abeta40 production ratio on both membrane thickness and

280 ixtures of the A2T mutant with the wild type Abeta40.

281 center of the three-fold symmetric wild-type Abeta40 fibril.

282 ious residues, while the Osaka and wild-type Abeta40 fibrils show a single or a predominant set of ch

283 and hydration of Arctic, Osaka and wild-type Abeta40 fibrils.

284 on and more immobilized water than wild-type Abeta40, indicating the influence of peptide structure o

285 teins to study the two major Abeta variants, Abeta40 and Abeta42.

286 roteins, and blood clots under flow in vitro Abeta40 also increased the stiffness of platelet-rich pl

287 e sensitive to chiral substitutions than was Abeta40 assembly.

288 from patients with t-AD and PCA-AD, whereas Abeta40 fibrils from r-AD samples exhibit a significantl

289 beta42 was just moderately decreased whereas Abeta40 levels were unchanged.

290 nown amyloid fibril forming regions, whereas Abeta40 forms an alternative but less populated antipara

291 magnitude larger than the frequency in which Abeta40 samples such structures.

292 IAPP self-assembly and hetero-assembly with Abeta40(42).

293 e in the production of Abeta38 compared with Abeta40 peptides, which is reminiscent of the effect of

294 microscopic rates for Abeta42 compared with Abeta40, but rather are due to a shift of more than one

295 sult in elevated neurotoxicity compared with Abeta40, but the molecular mechanism underlying this eff

296 ystal structure of ponezumab in complex with Abeta40 and found that the Abeta40 carboxyl moiety makes

297 re efficiently than Abeta40, consistent with Abeta40 being the primary species that accumulates in CA

298 man (rh) MMP-2 and MMP-9 were incubated with Abeta40 and Abeta42, and the resulting proteolytic fragm

299 r key residues of its cross-interaction with Abeta40(42) peptide.

300 trolling IAPP cross-peptide interaction with Abeta40(42) versus its amyloid self-assembly offer a mol

301 analysis reveals that in the absence of zinc Abeta40 aggregation is driven by a monomer-dependent sec