ライフサイエンスコーパス: Abeta40

1 Abeta40 aggregated into amyloid fibrils, whereas Abeta42

2 Abeta40 increased between 2 and 6 weeks (p=0.0001), and

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

4 Abeta40 was retrospectively measured in blood samples co

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

6 Abeta40/tau ratio was associated with Brief Visuospatial

7 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)],

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

9 These quasi-spherical Zn(2+)-Abeta40 oligomers irreversibly inhibit spontaneous neuro

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

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

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

13 Amyloid beta (Abeta) peptides, Abeta1-40 (Abeta40) and Abeta1-42 (Abeta42), have been implicated p

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

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

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

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

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

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 a significant increase (14 times) of Abeta42/Abeta40 ratios, with minimal effects on presenilin or th

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

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

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

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

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

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

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

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

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

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

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

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

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

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

41 Immunohistochemistry (IMHC) for AbetaPP, Abeta40, Abeta42 and pTau (epitope pT231) and ELISA for

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

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

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

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

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

47 sult in decrease of release of amyloidogenic Abeta40 fragments.

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

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

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

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

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

53 f Abeta species, particularly of Abeta38 and Abeta40.

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

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

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

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

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

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

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

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

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

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

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

65 metabolic labeling, we measured Abeta42 and Abeta40 production and clearance rates in the CNS of par

66 leads to production of secreted Abeta42 and Abeta40 respectively.

67 Clearance rates for both Abeta42 and Abeta40 were impaired in Alzheimer's disease compared wi

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

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

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

71 ficant increase in extracellular Abeta42 and Abeta40.

72 ta42 and the other binds to both Abeta42 and Abeta40.

73 ervation of the RPE are associated with anti-Abeta40/42 antibody immunotherapy and visual protection.

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

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

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

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

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

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

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

81 repeat region, whereas sites that bind both Abeta40 and Abeta42 are mainly in the extreme N-terminal

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

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

84 The C-terminal residues of both Abeta40 and Abeta42 display lower affinity for the proto

85 1 significantly increases the levels of both Abeta40 and Abeta42.

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

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

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

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

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

91 fragment of amyloid precursor protein (C99), Abeta40, and Abeta42 in 5XFAD mouse brains.

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

93 nhibited RAGE-mediated influx of circulating Abeta40 and Abeta42 into the brain.

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

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

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

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

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

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

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

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

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

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

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

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

106 polymorphism is intrinsic to the Arctic E22G Abeta40 sequence.

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

108 ar environment was mimicked by encapsulating Abeta40 monomers into reverse micelles.

109 ng in the decreased production of endogenous Abeta40 and an increased Abeta42/40 ratio.

110 onstrated that MT1-MMP can degrade exogenous Abeta40 and Abeta42.

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

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

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

114 .6- and 2.7-fold higher binding affinity for Abeta40 and Abeta42 in vitro, respectively, and a lower

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

116 e of a minimal antiaggregation chaperone for Abeta40.

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

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

119 eta42 and pTau (epitope pT231) and ELISA for Abeta40, Abeta42 and pT231 were performed on controls an

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

121 e binding to neurons, which requires H13 for Abeta40 but not for E22Delta or Abeta42.

122 ronal binding of these proteins as it is for Abeta40.

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

124 Mean ELISA values for Abeta40 and Abeta42 increased three- to four-fold in hyd

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

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

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

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

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

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

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

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

133 ase in Abeta42 levels with a 40% decrease in Abeta40 levels, leading to a significant increase (14 ti

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

135 erexpression resulted in >2-fold increase in Abeta40 levels as early as 4 mo of age.

136 A sustained increase in Abeta40 levels was seen at 12 mo of age in both CHAPS-so

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 e that turn nucleation is a critical step in Abeta40 fibril formation.

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

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

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

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

144 inding to the V domain of RAGE and inhibited Abeta40- and Abeta42-induced cellular stress in RAGE-exp

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

146 y 60-80% and significantly reduced insoluble Abeta40 and Abeta42 levels.

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

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

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

150 umulation of both secreted and intracellular Abeta40.

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

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

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

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

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

156 The modified Abeta40 was significantly more toxic than Abeta40.

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 2Delta, Abeta41E22Delta, and Abeta42 but not Abeta40.

160 Deletion of glutamate 22 of Abeta40 resulted in a 6-fold enhancement of PC12 neurona

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

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

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

164 t the primary domain for neuronal binding of Abeta40 involves histidine at position 13.

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

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

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

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

169 Furthermore, expression of Abeta40 or Abeta42 solely in the olfactory epithelium di

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

171 cluding >90% reductions in the generation of Abeta40, Abeta42, and the APP and Notch intracellular do

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 CR1-deficient mice had lower brain levels of Abeta40 and Abeta42 and reduced amyloid deposits.

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

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

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

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

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

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

183 with substantial reductions in production of Abeta40, Abeta42, and the APP and Notch intracellular do

184 -type PS1 while decreasing its production of Abeta40.

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

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

187 ety, resulting in in vivo brain reduction of Abeta40, is discussed.

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

189 The structured state of Abeta40 monomer has three more ordered segments at 14-18

190 Here we investigated the structures of Abeta40 monomer using a solid-support approach, in which

191 on of an antibody targeting the C termini of Abeta40 and Abeta42.

192 he in vivo conformation of the C-terminus of Abeta40 and the brain Abeta-lowering efficacy that we ob

193 specifically to the carboxyl (C)-terminus of Abeta40.

194 ligomer size distribution similar to that of Abeta40.

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

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

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

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

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

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

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

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

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

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

205 The Osaka Abeta40 mutant shows lower hydration and more immobilize

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

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

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

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

210 full-length Alzheimer amyloid beta peptides (Abeta40 and Abeta42) with the fully active form of insul

211 tration of ponezumab greatly elevates plasma Abeta40 levels in a dose-dependent fashion after adminis

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

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

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

215 asma concentrations of amyloid beta proteins Abeta40 and Abeta42 among 55 adults who had participated

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

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

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

219 rapalog-mediated proximity inducers reduced Abeta40 generation.

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

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

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

223 nvestigate the water interactions of several Abeta40 fibrils.

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

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

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

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

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

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

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

231 odulators (GSMs) act to preferentially spare Abeta40 production as well as Notch processing and signa

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

233 1 &Ala 42) that the non-pathological strain (Abeta40) lacks.

234 Synthetic Abeta40 preparations consisted of long straight fibrils;

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

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

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

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

239 for the C-terminal residues of Abeta42 than Abeta40, which might explain the former's higher propens

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 the two additional C-terminal residues that Abeta40 lacks.

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

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

249 onditions, however, EPR spectra suggest that Abeta40 monomers adopt both a disordered state and a str

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

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

252 their wild type homologues, and in both the Abeta40 and Abeta42 systems, the English and Tottori sub

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

254 that the naturally occurring function of the Abeta40 and Abeta42 peptides, which are causative agents

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

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

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

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

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

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 n residues of the Abeta42 strain compared to Abeta40.

268 In comparison to Abeta40, Abeta42 is more flexible and interacts through

269 Comparison to Abeta40-derived CTFs showed that the C-terminal dipeptid

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

271 vage significantly reduces APP processing to Abeta40.

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

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

274 ncrease in the amount of Abeta42 relative to Abeta40.

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

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

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

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

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

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

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

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

283 s significantly lower than that of wild-type Abeta40, presumably due to decreased oligomer population

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

285 e sensitive to chiral substitutions than was Abeta40 assembly.

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

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

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

289 mer using a solid-support approach, in which Abeta40 monomers are tethered on the solid support via a

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

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

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

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

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

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

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

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

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

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

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