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J. Biol. Chem., Vol. 277, Issue 22, 19506-19510, May 31, 2002
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From the
Received for publication, December 20, 2001, and in revised form, March 11, 2002
Amyloid plaques formed by aggregation of the
amyloid Amyloid Chemical analysis of human neuritic plaques reveals a complex mixture
of chemically altered A This study was aimed at investigating the consequences of Met-35
oxidation on the formation of small A Sample Preparation and Oxidation of Met-35--
A Mass Spectrometry--
A homebuilt instrument controlled the
direct infusion where helium gas at a pressure of 1.3 bars was used to
push the sample through a 30-cm fused silica capillary with an inner
diameter of 25 µm. One end of the capillary was lowered into the
sample, and the other end, coated by a conductive graphite/polymer
layer (20), was connected to ground, functioning as an electrospray needle. No sheath flow or nebulizing gas was used. The flow rate was
~40 nl/min. The ion source was coupled to an Analytica
atmosphere-vacuum interface (Analytica, Branford, CT). A potential
difference of 2.0-3.0 kV was applied across a distance of 3-5 mm
between the spraying needle and the inlet capillary. To confirm the
formation of A Analysis of A
Fig. 2 shows the C-terminal sequence of
A Aggregation Properties of A
After 12 h at 21 °C, ~50% of the 4.0 µM
A Aggregation Properties of A These results suggest that oxidation of Met-35 inhibits a
conformational switch of A From several structural predictions, Met-35 would be part of the
second The amphipathic nature of A In the experiments presented here, the ionization efficiencies and
charge state distributions of monomer and dimers did not differ
significantly between A Finally, the results also demonstrate the applicability of electrospray
ionization mass spectrometry to the study of the formation of small
amyloid peptide aggregates and their kinetics in the nanomolar to
micromolar range. Larger aggregates (decamers or larger) of A In conclusion, we believe these results emphasize the need for more
detailed molecular and mechanistic knowledge of the complex multistep
A We are grateful for the support and
encouragement of Professor Per Håkansson at the division of Ion
Physics, The Ångström Laboratory, Uppsala University.
*
This work was supported by the foundations of Knut and Alice
Wallenberg, Fredrik and Ingrid Thuring, Wilhelm and Martina Lundgren, Magnus Bergvall, Swedish Alzheimer, Syskonen Svensson, Gamla
Tjänarinnor, Clas Groschinsky, Åke Wiberg, Swedish Lundbeck, and
by Grant 13123 from the Swedish Medical Society and the Swedish Medical
Research Council.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
§
To whom correspondence may be addressed. Tel: 46-18-4713899;
Fax: 46-18-555736; E-mail: magnus.palmblad@angstrom.uu.se.
Published, JBC Papers in Press, March 23, 2002, DOI 10.1074/jbc.M112218200
2
A. Westlind-Danielsson, unpublished observations.
3
U. Bartenstein, Bachem AG, personal communication.
The abbreviations used are:
A
Oxidation of Methionine 35 Attenuates Formation of Amyloid
-Peptide 1-40 Oligomers*
§,
**
Division of Ion Physics, The Ångström
Laboratory, Uppsala University, Box 534, SE-751 21 Uppsala, Sweden,
¶ NEUROTEC, Karolinska Institute, Geriatric Medicine, Novum, KFC,
SE-141 86 Huddinge, Sweden, Institute of Clinical
Neuroscience, Department of Psychiatry and Neurochemistry,
Göteborg University, Sahlgrenska University
Hospital/Mölndal, SE-431 80 Mölndal, Sweden, and
** Department of Analytical Chemistry, Institute of
Chemistry, Uppsala University, Box 531, SE-751 21 Uppsala, Sweden
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
-peptide (A) are an intrinsic component of
Alzheimer disease pathogenesis. It has been suggested that oxidation of
methionine 35 in A has implications for Alzheimer disease, and it
has been shown that oxidation of Met-35 significantly inhibits
aggregation in vitro. In this study, the aggregational
properties of A-(1-40) before and after Met-35 oxidation were
investigated using electrospray ionization Fourier transform ion
cyclotron resonance mass spectrometry. The results show that
A-(1-40)Met-35(O) trimer and tetramer formation is significantly
attenuated as compared with A-(1-40). This suggests that oxidation
of Met-35 inhibits a conformational switch in A-(1-40) necessary
for trimer but not dimer formation. Random incorporation of
A-(1-40) and A-(1-40)Met-35(O) in homo- and heterooligomers could also be observed. This is the first report of an early
rate-limiting step in A-(1-40) aggregation. Slowing of the
fibrillization process at this early step is likely to support
prolonged solubility and clearance of A from brain and may
reduce disease progression.
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
-peptide
(A)1 is a 39-43 amino
acid long peptide derived from a larger transmembrane protein, the
amyloid precursor protein. A is the central component of
neuritic plaques in Alzheimer disease (AD) brain. A large number of
studies have focused on the structure, aggregational properties and
fibril formation (1-5), and neurotoxicity (6, 7) of A peptides and
their roles in AD.
deposited along with glycoproteins, glycolipids, and other ancillary components (3). Oxidized methionine, in position 35 (Met-35) of A, methionine sulfoxide
(Met-35(O)), has been detected in samples extracted from post-mortem AD
plaques (8). These findings have yet to be extended, eradicating the possibility of a post-mortem delay or a preparatively induced oxidation
artifact before in vivo extrapolation can be made. Few studies have explored the consequences of Met-35 oxidation on peptide
chemical characteristics or biological actions. There are, however,
some intriguing findings and some contradicting reports. Substituting
synthetic A1-42 with methionine sulfoxide Met-35(O) results in
enhanced A1-42-mediated cellular toxicity (9, 10).
Whether these actions are a consequence of attenuated (11) or
accelerated (10) fibril formation remains to be determined. A-(1-40)Met-35(O) is dramatically less prone to aggregation and fibril formation as compared with A-(1-40), shown in circular dichroism studies (12). This is also reflected by the inhibition of
conformational switching of A-(1-40)Met-35(O) from random coil to
-sheet, observed using millimolar peptide concentrations and NMR
(12). The inhibited aggregation can, however, be overcome by
increasing the concentration of
A-(1-40)Met-35(O).2 Using
size exclusion chromatography and oxidation of A-(1-40) with
H2O2, we have verified the attenuated fibril
formation associated with A-(1-40)Met-35(O). However, the
structural and conformational changes underlying this phenomenon have
not yet been identified. Peptide fibril formation is a complex
multistep reaction involving the transitional formation of numerous
oligomeric (13) and protofibrillar (14, 15) A species. Clarification
of what steps in the oligomerization cascade underlie the affected
aggregation rate of A-(1-40)Met-35(O) would not only increase our
understanding of the fibrillization reaction but also our understanding
of the forces determining peptide structure and folding. This could in
turn be important for understanding the potential toxicities of
different A species.
peptide oligomers and
also at attempting to find oxidation-mediated rate-limiting steps in
the fibrillization cascade of the Met-35(O)-modified A-(1-40)
peptide using a Fourier transform ion cyclotron resonance (FTICR) mass
spectrometer and a homebuilt electrospray device. Electrospray
ionization (ESI) mass spectrometry has been used previously to detect
and characterize A peptides in vitro (16) as well as
in vivo (17). Using gentle ESI conditions, small aggregates
of A-(1-40) in water can be transferred to the gas phase and
detected, making it possible to monitor the aggregation of A-(1-40)
over time (16). The oligomer distribution detected by ESI mass
spectrometry (16) is similar to that approached in the short
irradiation time limit of photo-induced cross-linking experiments (18).
An advantage in using the high resolving power of a 9.4 T FTICR
instrument is that homo- and heterooligomers of A-(1-40) and
A-(1-40)Met-35(O) can be resolved. Furthermore, the sensitivity of
the technique allows aggregation kinetics to be studied using nano- and
micromolar concentrations of A, more closely resembling the in
vivo situation (19).
MATERIALS AND METHODS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
-(1-40) was
obtained from Bachem (Bachem AG, Bubendorf, Switzerland). A 4.0 µM A-(1-40) solution was prepared in deionized water/acetic acid 99:1 (v/v), pH ~3. Immediately after dissolving the
peptide, an aliquot was taken out, and 30% (w/w) hydrogen peroxide in
water (Merck KGaA) was added to a final concentration of 2.7% (w/w).
The experiment was also reproduced using H2O and 2.7%
H2O2 solutions in absence of acetic acid.
Additional 2.0 µM solutions were prepared in 49.5:49.5:1
deionized water/acetonitrile/acetic acid solution (v/v/v) with and
without the addition of hydrogen peroxide to a final concentration of
2.7% (w/w).
-(1-40)Met-35(O), the peptide was sequenced by
collision-induced dissociation (21) in the capillary/skimmer region in
the ESI atmosphere/vacuum interface by raising the capillary potential from ~60 to ~270 V. All mass spectra were acquired using a Bruker Daltonics (Billerica, MA) BioAPEX-94e superconducting, 9.4 T FTICR mass
spectrometer (22) in broadband mode. Typically, 524,288 data
points were acquired, adding a minimum of 128 spectra (~3 min of
acquisition time).
RESULTS
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
-(1-40) in H2O--
Fig.
1 shows regions of superimposed mass
spectra of A-(1-40) and A-(1-40)Met-35(O) (methionine
sulfoxide) containing monomers, dimers, trimers, and tetramers of
A-(1-40) and A-(1-40)Met-35(O). The isotopic peaks of
[A-(1-40) + 2H+]2+ and the odd isotopic
peaks of [A-(1-40)2 + 4H+]4+
were resolved to the baseline as shown in the inset. The
isotopic clusters were shifted 16.00 Da per A-(1-40) monomer
oxidized. The unoxidized A-(1-40) spectrum was acquired between 41 and 95 min, and the A-(1-40)Met-35(O) spectrum was acquired between 100 and 116 min. The intensities were adjusted to compensate for the
different acquisition times. These long times are not necessary but
improve the signal-to-background ratio. Similar spectra taken between
20 and 30 min shows less than 1% A-(1-40)Met-35(O) in the
unoxidized A-(1-40) sample and less than 1% unoxidized
A-(1-40) in the oxidized sample. Putative dehydrated species (
18
Da) were also observed, likely to be the result of aspartimide
formation.3
View larger version (36K):
[in a new window]
Fig. 1.
Excerpts from superimposed mass spectra of
4.0 µM
A -(1-40) before and after oxidation induced
by H2O2 showing monomers, dimers, trimers, and
tetramers of A-(1-40) and
A-(1-40)Met-35(O). The isotopic peaks of
[M + 2H+]2+ and the odd isotopic peaks of
[M2 + 4H+]4+ were resolved to the
baseline (inset). The isotopic clusters were shifted 16.00 mass units per A-(1-40) monomer, corresponding to one extra
16O.
-(1-40)Met-35(O) read from a series of quadruply charged
b-ions (23) from the quadruply charged parent ion
[A-(1-40)Met-35(O) + 4H+]4+ resulting
from collision-induced dissociation in the capillary/skimmer region.
The b-ions covering residues 3-40 could be identified in
this spectrum, b
peptides while studying aggregation kinetics using the FTICR mass spectrometer.
View larger version (33K):
[in a new window]
Fig. 2.
The C-terminal part of the sequence of
A -(1-40)Met-35(O) can be read by comparing
quadruply charged b-ions and the quadruply charged
parent ion. A b-ion series covering residues 3-40
could be found in this spectrum,
b
-(1-40) and A-(1-40)Met(O) in
H2O--
After dissolving A-(1-40) in H2O
or in 2.7% H2O2 in H2O, monomers
and dimers of A-(1-40) and A-(1-40)Met-35(O) could be detected
in the first acquired mass spectra. The monomer and dimer signal
intensities were the same for A-(1-40) and A-(1-40)Met-35(O) (Fig. 3). Trimers
A-(1-40)3 and tetramers A-(1-40)4 could
also be detected in the first spectra of A-(1-40) in
H2O. However, trimers A-(1-40)Met-35(O)3
and tetramers A-(1-40)Met-35(O)4 were not found in the
first spectra of A-(1-40) in 3% H2O2 or after 27-32 min (Fig. 3). After >100 min of incubation, the
A-(1-40) and A-(1-40)Met-35(O) trimer and tetramer signals were
also similar except for the mass shift of 16.00 Da per A-(1-40)
monomer caused by oxidation of Met-35. This lag phase was associated
with the formation of A-(1-40)Met-35(O)3 from
A-(1-40)Met(O) and A-(1-40)Met-35(O)2 and has not
been reported previously, although lag phases in A aggregation have
been observed in A-(1-40) and A-(1-42) mixtures (25, 26).
A-(1-40) and A-(1-40)Met-35(O) could be detected at 4.0 µM, 40 nM, 4.0 nM, and 400 pM concentrations; however, trimers and tetramers could
only be detected at 4.0 µM, whereas dimers could still be
detected at 40 nM. As a comparison, the concentration of
A-(1-40) is about 10 ng/ml or 2.3 nM in cerebrospinal fluid (27).
View larger version (41K):
[in a new window]
Fig. 3.
Mass spectra of 4.0 µM A -(1-40)
and A-(1-40)Met-35(O) acquired shortly after
dissolving A-(1-40) in H2O
(a and c, acquired after 20-25 min)
and H2O and 2.7% H2O2
(b and d, acquired after 27-32
min). Monomer and dimer signal intensities are comparable between
the two spectra (a and b), whereas no trimer (or
tetramer) could be detected in the A-(1-40)Met-35(O) spectrum
(d). After incubation in room temperature for 100 min,
trimer (and tetramer) signal could be detected also in the
A-(1-40)Met-35(O) spectrum (h, acquired after 100-116
min). Spectra e and g were acquired after 41 and
95 min. The monomer and dimer signal is still comparable in the two
spectra (e and f). The spectra e-h
were scaled to compensate for the different accumulation times.
-(1-40) had been oxidized in the absence of hydrogen peroxide
(Fig. 4). The A-(1-40) dimers were
distributed ~0.25:0.5:0.25 among A-(1-40)2,
A-(1-40)A-(1-40)Met-35(O), and
A-(1-40)Met-35(O)2 (Fig.
5), indicating random incorporation of
A-(1-40) and A-(1-40)Met-35(O) in dimers after 12 h.
Similarly, a binomial distribution 0.125:0.375:0.375:0.125 is
consistent with the measured signal of A-(1-40) trimers (Fig.
6), although only
A-(1-40)2A-(1-40)Met-35(O) and
A-(1-40)A-(1-40)Met-35(O)2 have significant
signal-to-background ratios to be detected in this spectrum. This
indicates the random incorporation of A-(1-40) and
A-(1-40)Met-35(O) also in heterotrimers formed after 12 h.
View larger version (13K):
[in a new window]
Fig. 4.
Spontaneous oxidation of Met-35 rendering
about half of the A -(1-40) (49.5% if adding
the most abundant charge states 3+ and 4+)
oxidized after 12 h in room temperature (21 °C).
View larger version (29K):
[in a new window]
Fig. 5.
Mass spectrum showing the distribution of
dimeric forms of A -(1-40) and
A-(1-40)Met-35(O). If A-(1-40) and
A-(1-40)Met-35(O) are randomly incorporated into dimers, a
0.25:0.5:0.25, or binomial, distribution of A-(1-40)2,
A-(1-40)A-(1-40)Met-35(O), and
A-(1-40)Met-35(O)2 would be expected. In this spectrum,
the distribution is 0.290:0.446:0:263 and thus consistent with the
assignment of little or no importance of oxidization of Met-35 in the
formation of dimers at longer incubation times.
View larger version (44K):
[in a new window]
Fig. 6.
Distribution of
A -(1-40)2A-(1-40)Met-35(O)
and
A-(1-40)A-(1-40)Met-35(O)2
after 12 h, indicating little or no preference between
A-(1-40) and
A-(1-40)Met-35(O) in heterotrimers at longer
incubation times. The inset shows the local
autocorrelation of the spectrum in a window containing
A-(1-40)2A-(1-40)Met-35(O), indicating the presence
of a 5+ species.
-(1-40) in H2O and
Organic Solvent--
In the absence of an oxidizing agent, different
charge states of dimers, trimers, tetramers, and pentamers of
A-(1-40) could be detected in the mass spectra of A-(1-40) in
low micromolar concentrations in a typical electrospray solution of
49.5% ACN, 49.5% H2O, and 1% HAc (v/v/v), cf.
Shen and Murphy (28). The pentameric form has not been reported
previously in mass spectrometric studies. Aggregates could be
selectively removed from the spectra by collisional heating in the
hexapole ion trap in the ESI interface (29) without significant
fragmentation or loss of monomer. After complete (>99%) oxidization
of Met-35, no aggregates could be found in the mass spectra of
A-(1-40)Met(O) in H2O2 and acetonitrile even after several hours of incubation.
DISCUSSION
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
-(1-40) necessary for trimer formation but also that this conformational change does not significantly affect
the formation of dimers of A-(1-40) at low micromolar concentrations. Whether this switch occurs primarily in free
monomers or in dimers or whether dimers formed in one A molecule can
go on to induce the same switch in other A molecules remains to be
investigated. The random incorporation of A-(1-40) and
A-(1-40)Met-35(O) in homo- and heterodimers indicates that
oxidization of Met-35 is of little or no importance in the
formation of dimers. This is also consistent with the predicted
structure of A-(1-42) dimers where the Met-35 side chains are not
located in the dimer interface (30).
-helix of the A-(1-40) molecule, comprising amino acid
residues 28-36 (31-33). Reportedly, A-(1-40) shows predominant -helical structure at conditions that are thought to mimic the membrane environment, including SDS and trifluoroethanol (31, 33, 34).
Previously, -helix formation of A was detected in water solution
(35) but not known to be a prerequisite for -sheet formation.
However, recently careful temporal CD studies by Kirkitadze et
al. (36) revealed that -helical structure is formed in water
solution by 18 biologically relevant forms of the A peptide
(including A-(1-40)) as a transitory structure en route
to the -sheet structure. Interestingly, Kallberg et al.
(37) have identified the so-called / discordance as a predictor
of -amyloid formation, including the A peptide, which further
strengthens the -helix
-sheet transition hypothesis. A is,
like SDS, an amphipathic molecule, and evidence was recently presented
that it forms micelle-like structures (38), previously predicted to
comprise a step in the fibrillization process (39). These allegedly
constitute centers for fibril nucleation (38). One can therefore
envision that, similarly to its dissolution by SDS, A forms
-helix-competent environments on its own accord, in micell-like
aggregates, once it reaches the critical "micellar" concentration
needed for this structural transition.
stems from its relatively polar
N-terminal and extremely hydrophobic C-terminal region. There is also
the central hydrophobic core, composed of amino acids 17-21. These
hydrophobic regions, and in particular the C-terminal residues, Ile-41
and Ala-42 of the A1-42 peptide (36), are critical determinants of
the aggregation rate (40, 41). The oxidation may also change the
stability of the second -helix. However, the -helix structure of
A has been detected just prior to maximum -sheet formation when
preparations are rich in higher molecular weight aggregates (36).
Although the effect of Met-35(O) may be substantial in these instances,
it is not likely to provide an explanation of our observations given
the low concentrations and short time frames used in this work
and when low molecular weight oligomers have been the focus of
attention. Therefore, the driving force for the association of these
small oligomeric structures may be more dependent on hydrophobic
interactions than on secondary structural driving forces. A dimer
methionine sulfoxide groups pointing outwards, as suggested by
molecular modeling (30) and indirectly supported by our observations,
would reduce the total hydrophobic surface available for further
molecular association. Interestingly, Shen and Murphy (28) have
observed faster fibril growth rates in acidic acetonitrile/water
solution. The secondary structure of dimers and trimers remains to be
determined using direct methods such as NMR, and the discussion on
-helical contents has to be considered in this context.
-(1-40) and A-(1-40)Met-35(O) and
therefore could be expected to be similar for trimers and tetramers as
well, which is also supported by the fact that trimer and tetramer
signal intensities are comparable after the initial lag phase. One
should be cautious not to draw conclusions from the measurements of
single charge states as charge state distribution can (and does, at
least to a small degree) change upon oxidation of Met-35. The
alteration of ionization efficiency and charge state distribution are
possible sources of artifacts in electrospray ionization and could be
caused by slight shifts in pH or altered potentials in the
atmosphere/vacuum interface due to contamination.
peptides should be possible to detect in mass spectrometers of this
type if present in micromolar concentrations (22), provided they
survive the transition from liquid to gas phase and provided that
stable electrospray conditions can be obtained in such solutions.
fibrillization reaction to rapidly provide a more profound
understanding of both cause and effect of A-mediated actions
in vitro and also in vivo. In addition, the
post-translational Met-35 modification, if it is effectuated in
vivo, provides an intriguing possibility for the brain
involving rerouting A from a potential protofibrillar/fibrillar
pathway to a pathway that opens up better prospects of keeping low
molecular weight A species in solution longer, thereby increasing
the likelihood of proteolysis and clearance while decreasing the risks
of deposition. The growing scientific foundation for a role of
oxidative stress in AD brains (42) along with the recent shift in focus
from the role of fibrillar to prefibrillar (13) and protofibrillar (43)
A species in the pathogenesis of AD make these observations
particularly intriguing.
ACKNOWLEDGEMENT
FOOTNOTES
A senior researcher at the Swedish Research Council
(VR). To whom correspondence may be addressed. Tel.: 46-18-4713675;
Fax: 46-15-4713692; E-mail: jonas.bergquist@kemi.uu.se.
ABBREVIATIONS
, amyloid
-peptide;
AD, Alzheimer disease;
FTICR, Fourier transform ion
cyclotron resonance;
ESI, electrospray ionization.
REFERENCES
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
1.
Jarrett, J. T.,
and Lansbury, P. T., Jr.
(1993)
Cell
73,
1055-1058[CrossRef][Medline]
[Order article via Infotrieve]
2.
Lansbury, P. T. J.,
Costa, P. R.,
Griffiths, J. M.,
Simon, E. J.,
Auger, M.,
Halverson, K. J.,
Kocisko, D. A.,
Hendsch, Z. S.,
Ashburn, T. T.,
Spencer, R. G.,
Tidor, B.,
and Griffin, R. G.
(1995)
Nat. Struct. Biol.
2,
990-998[CrossRef][Medline]
[Order article via Infotrieve]
3.
Kisilevsky, R.,
and Fraser, P. E.
(1997)
Crit. Rev. Biochem. Mol. Biol.
32,
361-404[Medline]
[Order article via Infotrieve]
4.
Teplow, D. B.
(1998)
Amyloid
5,
121-142[Medline]
[Order article via Infotrieve]
5.
Huang, T. H.,
Yang, D. S.,
Fraser, P. E.,
and Chakrabartty, A.
(2000)
J. Biol. Chem.
275,
36436-36440 6.
Iversen, L. L.,
Mortishire-Smith, R. J.,
Pollack, S. J.,
and Shearman, M. S.
(1995)
Biochem. J.
311,
1-16
7.
Harkany, T.,
Abraham, I.,
Konya, C.,
Nyakas, C.,
Zarandi, M.,
Penke, B.,
and Luiten, P. G.
(2000)
Rev. Neurosci.
11,
329-382[CrossRef][Medline]
[Order article via Infotrieve]
8.
Kuo, Y. M.,
Kokjohn, T. A.,
Beach, T. G.,
Sue, L. I.,
Brune, D.,
Lopez, J. C.,
Kalback, W. M.,
Abramowski, D.,
Sturchler-Pierrat, C.,
Staufenbiel, M.,
and Roher, A. E.
(2001)
J. Biol. Chem.
276,
12991-12998 9.
Pike, C. J.,
Walencewicz-Wasserman, A. J.,
Kosmoski, J.,
Cribbs, D. H.,
Glabe, C. G.,
and Cotman, C. W.
(1995)
J. Neurochem.
64,
253-265[Medline]
[Order article via Infotrieve]
10.
Seilheimer, B.,
Bohrmann, B.,
Bondolfi, L.,
Muller, F.,
Stuber, D.,
and Dobeli, H.
(1997)
J. Struct. Biol.
119,
59-71[CrossRef][Medline]
[Order article via Infotrieve]
11.
Snyder, S. W.,
Ladror, U. S.,
Wade, W. S.,
Wang, G. T.,
Barrett, L. W.,
Matayoshi, E. D.,
Huffaker, H. J.,
Krafft, G. A.,
and Holzman, T. F.
(1994)
Biophys. J.
67,
1216-1228 12.
Watson, A. A.,
Fairlie, D. P.,
and Craik, D. J.
(1998)
Biochemistry
37,
12700-12706[CrossRef][Medline]
[Order article via Infotrieve]
13.
Klein, W. L.,
Krafft, G. A.,
and Finch, C. E.
(2001)
Trends Neurosci.
24,
219-224[CrossRef][Medline]
[Order article via Infotrieve]
14.
Walsh, D. M.,
Lomakin, A.,
Benedek, G. B.,
Condron, M. M.,
and Teplow, D. B.
(1997)
J. Biol. Chem.
272,
22364-22372 15.
Harper, J. D.,
Wong, S. S.,
Lieber, C. M.,
and Lansbury, P. T.
(1997)
Chem. Biol.
4,
119-125[CrossRef][Medline]
[Order article via Infotrieve]
16.
Chen, X. G.,
Brining, S. K.,
Nguyen, V. Q.,
and Yergey, A. L.
(1997)
FASEB J.
11,
817-823[Abstract]
17.
Golde, T. E.,
Eckman, C. B.,
and Younkin, S. G.
(2000)
Biochim. Biophys. Acta
1502,
172-187[Medline]
[Order article via Infotrieve]
18.
Bitan, G.,
Lomakin, A.,
and Teplow, D. B.
(2001)
J. Biol. Chem.
276,
35176-35184 19.
Sennvik, K.,
Fastbom, J.,
Blomberg, M.,
Wahlund, L. O.,
Winblad, B.,
and Benedikz, E.
(2000)
Neurosci. Lett.
278,
169-172[CrossRef][Medline]
[Order article via Infotrieve]
20.
Nilsson, S.,
Wetterhall, M.,
Bergquist, J.,
Nyholm, L.,
and Markides, K. E.
(2001)
Rapid Commun. Mass Spectrom.
15,
1997-2000[CrossRef][Medline]
[Order article via Infotrieve]
21.
Hayes, R. N.,
and Gross, M. L.
(1990)
Methods Enzymol.
193,
237-263[Medline]
[Order article via Infotrieve]
22.
Palmblad, M.,
Håkansson, K.,
Håkansson, P.,
Feng, X.,
Cooper, H. J.,
Giannakopulos, A. E.,
Green, P. S.,
and Derrick, P. J.
(2000)
Eur. Mass Spectrom.
6,
267-275
23.
Roepstorff, P.,
and Fohlman, J.
(1984)
Biol. Mass Spectrom.
11,
601
24.
Palmblad, M.,
Wetterhall, M.,
Markides, K.,
Håkansson, P.,
and Bergquist, J.
(2000)
Rapid Commun. Mass Spectrom.
14,
1029-1034[CrossRef][Medline]
[Order article via Infotrieve]
25.
Hasegawa, K.,
Yamaguchi, I.,
Omata, S.,
Gejyo, F.,
and Naiki, H.
(1999)
Biochemistry
38,
15514-15521[CrossRef][Medline]
[Order article via Infotrieve]
26.
Westlind-Danielsson, A.,
and Arnerup, G.
(2001)
Biochemistry
40,
14736-14743[CrossRef][Medline]
[Order article via Infotrieve]
27.
Mehta, P. D.,
Pirttila, T.,
Mehta, S. P.,
Sersen, E. A.,
Aisen, P. S.,
and Wisniewski, H. M.
(2000)
Arch. Neurol.
57,
100-105 28.
Shen, C. L.,
and Murphy, R. M.
(1995)
Biophys. J.
69,
640-651 29.
Håkansson, K.,
Axelsson, J.,
Palmblad, M.,
and Håkansson, P.
(2000)
J. Am. Soc. Mass Spectrom.
11,
210-217[CrossRef][Medline]
[Order article via Infotrieve]
30.
Chaney, M. O.,
Webster, S. D.,
Kuo, Y. M.,
and Roher, A. E.
(1998)
Protein Eng.
11,
761-767 31.
Barrow, C. J.,
Yasuda, A.,
Kenny, P. T.,
and Zagorski, M. G.
(1992)
J. Mol. Biol.
225,
1075-1093[CrossRef][Medline]
[Order article via Infotrieve]
32.
Shao, H.,
Jao, S., Ma, K.,
and Zagorski, M. G.
(1999)
J. Mol. Biol.
285,
755-773[CrossRef][Medline]
[Order article via Infotrieve]
33.
Coles, M.,
Bicknell, W.,
Watson, A. A.,
Fairlie, D. P.,
and Craik, D. J.
(1998)
Biochemistry
37,
11064-11077[CrossRef][Medline]
[Order article via Infotrieve]
34.
Soto, C.,
Castano, E. M.,
Frangione, B.,
and Inestrosa, N. C.
(1995)
J. Biol. Chem.
270,
3063-3067 35.
Walsh, D. M.,
Hartley, D. M.,
Kusumoto, Y.,
Fezoui, Y.,
Condron, M. M.,
Lomakin, A.,
Benedek, G. B.,
Selkoe, D. J.,
and Teplow, D. B.
(1999)
J. Biol. Chem.
274,
25945-25952 36.
Kirkitadze, M. D.,
Condron, M. M.,
and Teplow, D. B.
(2001)
J. Mol. Biol.
312,
1103-1119[CrossRef][Medline]
[Order article via Infotrieve]
37.
Kallberg, Y.,
Gustafsson, M.,
Persson, B.,
Thyberg, J.,
and Johansson, J.
(2001)
J. Biol. Chem.
276,
12945-12950 38.
Yong, W.,
Lomakin, A.,
Kirkitadze, M. D.,
Teplow, D. B.,
Chen, S. H.,
and Benedek, G. B.
(2002)
Proc. Natl. Acad. Sci. U. S. A.
99,
150-154 39.
Lomakin, A.,
Teplow, D. B.,
Kirschner, D. A.,
and Benedek, G. B.
(1997)
Proc. Natl. Acad. Sci. U. S. A.
94,
7942-7947 40.
Kirschner, D. A.,
Inouye, H.,
Duffy, L. K.,
Sinclair, A.,
Lind, M.,
and Selkoe, D. J.
(1987)
Proc. Natl. Acad. Sci. U. S. A.
84,
6953-6957 41.
Tjernberg, L. O.,
Näslund, J.,
Lindqvist, F.,
Johansson, J.,
Karlstrom, A. R.,
Thyberg, J.,
Terenius, L.,
and Nordstedt, C.
(1996)
J. Biol. Chem.
271,
8545-8548 42.
Butterfield, D. A.,
Yatin, S. M.,
and Link, C. D.
(1999)
Ann. N. Y. Acad. Sci.
893,
265-268[CrossRef][Medline]
[Order article via Infotrieve]
43.
Nilsberth, C.,
Westlind-Danielsson, A.,
Eckman, C. B.,
Condron, M. M.,
Axelman, K.,
Forsell, C.,
Stenh, C.,
Luthman, J.,
Teplow, D. B.,
Younkin, S. G.,
Näslund, J.,
and Lannfelt, L.
(2001)
Nat. Neurosci.
4,
887-893[CrossRef][Medline]
[Order article via Infotrieve]
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