Combined Analysis of CSF Tau, Aβ42, Aβ1–42% and Aβ1–40% in Alzheimer's Disease, Dementia with Lewy Bodies and Parkinson's Disease Dementia

Abstract

We studied the diagnostic value of CSF Aβ42/tau versus low Aβ1-42% and high Aβ1-40(ox)% levels for differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), respectively. CSF of 45 patients with AD, 15 with DLB, 21 with Parkinson's disease dementia (PDD), and 40 nondemented disease controls (NDC) was analyzed by Aβ-SDS-PAGE/immunoblot and ELISAs (Aβ42 and tau). Aβ42/tau lacked specificity in discriminating AD from DLB and PDD. Best discriminating biomarkers were Aβ1-42% and Aβ1-40(ox)% for AD and DLB, respectively. AD and DLB could be differentiated by both Aβ1-42% and Aβ1-40(ox)% with an accuracy of 80% at minimum. Thus, we consider Aβ1-42% and Aβ1-40(ox)% to be useful biomarkers for AD and DLB, respectively. We propose further studies on the integration of Aβ1-42% and Aβ1-40(ox)% into conventional assay formats. Moreover, future studies should investigate the combination of Aβ1-40(ox)% and CSF alpha-synuclein for the diagnosis of DLB.

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International Journal of Alzheimer’s Disease
Volume 2010, Article ID 761571, 7pages
doi:10.4061/2010/761571
Research Article
Combined Analysis of CSF Tau, Aβ42, Aβ1–42% and Aβ1–40ox%in
Alzheimer’s Disease, Dementia with Lewy Bodies and Parkinson’s
Disease Dementia
Mirko Bibl,1Hermann Esselmann,2Piotr Lewczuk,3Claudia Trenkwalder,4Markus Otto,5
Johannes Kornhuber,3Jens Wiltfang,2and Brit Mollenhauer4
1Department of Psychiatry, Psychotherapy and Addiction Medicine, Kliniken Essen-Mitte, University of Duisburg-Essen,
Henricistrasse 92, 45136 Essen, Germany
2Department of Psychiatry, Psychotherapy, Rheinische Kliniken Essen, University of Duisburg-Essen, 45147 Essen, Germany
3Department of Psychiatry and Psychotherapy, University of Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany
4Paracelsus-Elena Klinik, University of Goettingen, 34128 Kassel, Germany
5Institute for Neurology, University of Ulm, 89075 Ulm, Germany
Correspondence should be addressed to Mirko Bibl, m.bibl@kliniken-essen-mitte.de
Received 15 April 2010; Revised 8 July 2010; Accepted 11 July 2010
Academic Editor: Lucilla Parnetti
Copyright © 2010 Mirko Bibl et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
We studied the diagnostic value of CSF Aβ42/tau versus low Aβ1–42% and high Aβ1–40ox%levelsfordifferential diagnosis of
Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB), respectively. CSF of 45 patients with AD, 15 with DLB, 21 with
Parkinson’s disease dementia (PDD), and 40 nondemented disease controls (NDC) was analyzed by Aβ-SDS-PAGE/immunoblot
and ELISAs (Aβ42 and tau). Aβ42/tau lacked specificity in discriminating AD from DLB and PDD. Best discriminating biomarkers
were Aβ1–42% and Aβ1–40ox % for AD and DLB, respectively. AD and DLB could be differentiated by both Aβ1–42% and Aβ1–
40ox% with an accuracy of 80% at minimum. Thus, we consider Aβ1–42% and Aβ1–40ox%tobeusefulbiomarkersforADand
DLB, respectively. We propose further studies on the integration of Aβ1–42% and Aβ1–40ox% into conventional assay formats.
Moreover, future studies should investigate the combination of Aβ1–40ox % and CSF alpha-synuclein for the diagnosis of DLB.
1. Introduction
Reduced amyloid-β(Aβ) 42 peptide concentrations and
elevated tau levels in cerebrospinal fluid (CSF) represent sup-
portive features of Alzheimer’s dementia (AD) diagnosis [1].
These biomarkers have shown their major diagnostic value in
comparison of AD to controls, but overlapping values have
hampered sufficient diagnostic accuracy in differentiating
other kinds of dementia, especially vascular dementias and
dementia with Lewy bodies [2]. The specificity of Aβ42 in
the differential diagnosis of AD and other dementias could be
improved by measuring the relative Aβ1–42 concentration in
CSF as compared to the sum of the peptides Aβ1–40, Aβ1–
38, Aβ1–37, Aβ1–39, and oxidized Aβ1–40 (Aβ1–40ox)asa
percentage value (Aβ1–42%) [3]. Moreover, the percentage
value of Aβ1–40ox (Aβ1–40ox%) has been proposed as a
potentially helpful CSF biomarker in diagnosing DLB [3,4].
This study investigates the additional diagnostic value
of these novel CSF biomarker candidates as compared to
the well-acknowledged combined analysis of tau and Aβ42
in differentiating the dementias AD, DLB, and PDD. For
this purpose, CSF levels of tau, Aβ42, Aβ1–42%, and
Aβ1–40ox% were determined in CSF of 45 patients with
probable AD, 15 with probable DLB, 21 with PDD and
40 nondemented disease controls (NDC). Their respective
diagnostic accuracies for each relevant differential diagnostic
quest were analyzed.
2. Patients and Methods
2.1. Patients. We investigated 121 CSF samples that were
referred to our laboratory between 1999 and 2004. CSF
concentrations of tau, Aβ42, Aβ1–42%, and Aβ1–40 were
measured. Aliquots of these samples had been studied

2 International Journal of Alzheimer’s Disease
previously under another objective and focussing a distinct
issue of differentially diagnosing dementias [3].
CSF of patients with DLB and PDD, respectively, came
from the Paracelsus-Elena Klinik, Kassel, a hospital spe-
cialized in the management of movement disorders. CSF
samples of AD patients and nondemented disease controls
came from the memory clinic and from wards at Goettingen
University.
A psychiatrist and a neurologist rendered diagnoses
based on thorough clinical examination, neuropsychological
assessment, clinical records, and best clinical judgment. The
investigators were blinded to the neurochemical outcome
measures. Investigations were carried out with the informed
consent of patients or their authorized caregiver. The study
was conducted under the guidelines of the Declaration of
Helsinki [5] and approved by the ethics committee of the
University of Goettingen and Hessen.
The nondemented disease controls consisted of two
subgroups.
2.1.1. Neurological Diseases without Dementia Syndrome.
The 15 patients (6 women and 9 men) underwent lum-
bar puncture for routine investigation of central nervous
affection. The patients were suffering from Parkinson’s
disease (n=6), polyneuropathy (n=2), genetically
reconfirmed Huntington’s disease (n=2), spinocerebellar
ataxia (n=2), peripheral facial nerve palsy (n=1),
autosomal dominant hereditary spastic spinal palsy (n=
1) and amyotrophic lateral sclerosis (n=1).The Mini
Mental Status Examination (MMSE) score in patients with
cognitive complaints (n=8) was 28.0 ±1.5 (mean ±SD).
None of these patients displayed clinical features of dementia
syndrome DSM IV or NINCDS-ADRDA criteria [6]. Age of
this subgroup was 66.7 ±6.9 years (mean ±SD).
2.1.2. Depressive Cognitive Complainers. The 25 depressive
patients (16 women and 9 men) underwent lumbar puncture
for differential diagnosis of cognitive complaints during
the course of disease. The diagnosis of depression was
made according to the criteria of DSM IV and cognitive
impairment was assessed by MMSE at minimum. Patients
with persistent cognitive decline for more than six months,
MMSE score below 26 or clear focal atrophy in brain imaging
(CT or MRI) were excluded. Age of this subgroup was 63.2 ±
10.4 years (mean ±SD).
2.1.3. Patients with Alzheimer’s Disease. 45 patients (27
women and 18 men) fulfilled DSM IV criteria and NINCDS-
ADRDA criteria for clinical diagnosis of AD [6]. Struc-
tural (CT or MRI) or functional (SPECT or PET) brain
imaging displayed global cortical atrophy, or temporal,
parietotemporal, or frontotemporal focal atrophy, or marked
hypometabolism of these regions.
2.1.4. Patients with Dementia with Lewy Bodies (DLB) and
Parkinson’s Disease Dementia (PDD). Dementia with Lewy
bodies (DLB, n=15, 3 women and 12 men) was diagnosed
according to the consensus criteria [7]. Patients presented
with at least two core features according to the criteria
and with parkinsonism less than one year before onset of
dementia. Enrolled patients were hospitalized for several days
to evaluate fluctuating cognition, extrapyramidal symptoms,
and visual hallucinations.
Parkinson’s disease dementia (PDD) was diagnosed in 21
patients (6 women and 15 men) according to UK Parkinson’s
Disease Society Brain Bank clinical diagnostic criteria for
idiopathic Parkinson’s disease and the consensus criteria
[7,8]. All patients presented parkinsonism at least one year
before onset of dementia.
ThemeanageandMMSEscoreofpatientgroupsare
giveninTable1.
2.2. Test Methods
2.2.1. Preanalytical Treatment of CSF. CSF was drawn by
lumbar puncture into polypropylene vials and centrifuged
(1000 g, 10 min, 4◦C). Aliquots of 200 μLwerekeptatroom
temperature for a maximum of 24 hours before storage
at −80◦CforsubsequentAβ-SDS-PAGE/immunoblot. The
samples were not thawed until analysis. The freezers had an
automatic temperature control and alarm system, so that
relevant temperature changes during the time of storage can
be excluded. CSF for total Aβand tau ELISA analysis was
stored at +4◦C and analyzed within two days. The protocol
of preanalytical CSF handling was harmonized between the
two centres of Goettingen and Kassel.
2.2.2. ELISA for Total-Tau and Aβ1–42. The ELISAs Innotest
hTAUAntigenELISAandInnotestβ-Amyloid(1−42), ELISA
Innogenetics (Ghent, Belgium) served for quantification
of CSF tau and Aβ1–42, respectively. Both ELISAs were
conducted according to published standard methods [9].
2.3. Aβ-SDS-PAGE/Immunoblot. Aβpeptide patterns were
analyzed by Aβ-SDS-PAGE/immunoblot. For separation of
Aβpeptides and subsequent detection, 10 μlofuncon-
centrated CSF were boiled in a sample buffer for SDS-
PAG E , a n d A β-SDS-PAGE/immunoblot was conducted as
published elsewhere [10,11]. CSF samples of each individual
patient were run as triplicates. Bands were quantified from
individual blots of each patient relative to a four point
dilution series of synthetic Aβpeptides using a charge
coupled device camera. The detection sensitivity was 0.6
pg (Aβ1–38, Aβ1–40) and 1 pg (Aβ1–37, Aβ1–39, Aβ1–42),
respectively. Signal acquisition was linear within a range of
3.8 magnitudes of order [10]. The inter- and intra-assay
coefficients of variation for 20 to 80 pg of synthetic Aβ
peptides were below 10% [10,11].
2.4. Statistical Analysis. Aβpeptide and tau levels were
expressed as absolute values (ng/ml). The data on Aβpeptide
levels were obtained from individual blots of each patient.
Aβpeptide values were determined in absolute (ng/ml) and
percentage values relative to the sum of all investigated Aβ
peptides (Aβ1–X%). We have characterized patient groups
by mean and standard deviation (SD).

International Journal of Alzheimer’s Disease 3
Tab l e 1: Age, MMSE, Total tau, Aβ42, Aβ1–42%, and Aβ1–40ox% in the CSF of the diagnostic groups.
Diagnosis NDC (n=40) AD (n=45) DLB (n=15) PDD (n=21)
mean ±SD mean ±SD mean ±SD mean ±SD
Age 64.5 ±9.3 70.9 ±9.2 71.4 ±7.6 73.2 ±7.2
MMSE 28.6 ±1.4 19.4 ±5.8 19.2 ±3.0 18.1 ±7.2
Total tau (ELISA)10.23 ±0.14 0.62 ±0.34 0.37 ±0.29 0.31 ±0.24
Aβ1–42 (ELISA)10.79 ±0.27 0.41 ±0.14 0.37 ±0.17 0.51 ±0.22
Aβ42/Tau (ELISA)14.74 ±3.03 0.87 ±0.58 1.63 ±1.35 3.16 ±2.72
Aβ1–42% (Aβ-SDS-PAGE/immunoblot)211.65 ±3.53 4.38 ±0.89 7.13 ±2.13 7.54 ±2.07
Aβ1–42% (Aβ-SDS-PAGE/immunoblot)20.77 ±0.5 0.88 ±0.27 1.78 ±0.70 1.05 ±0.48
1Aβpeptide concentrations as measured by ELISA (ng/ml or ratio)
2Aβpeptide values of Aβ1–42 and Aβ1–40ox, respectively, relative to the sum of all measurable Aβpeptides in the Aβ-SDS-PAGE/ immunoblot
The Mann-Whitney U-test was employed for compar-
isons of diagnostic groups. Multiple comparisons were not
performed. Correlations of measured values were estimated
by Spearman’s Rho. The two-sided level of significance was
taken as P<.05.The global diagnostic accuracies were
assessed by the area under the curve (AUC) of receiver
operating characteristic curve (ROC). Cutoffpoints were
determined at the maximum Youden index [12], providing
asensitivityof≥80%. The statistical software package SPSS,
version 12.0, was used for computations.
3. Results
3.1. Test Results. The mean age of NDC was significantly
younger than each of the dementia groups (P<5×10−2).
The dementia groups did not significantly differ from each
other in age. The mean MMSE score did not significantly
differ between the dementia groups.
Patients with neurological diseases without dementia
syndrome exhibited higher levels of CSF Aβ1–40ox%(P=
6.1×10−4)andlowerlevelsofAβ1–42 (P=1.3×10−2)
than depressive cognitive complainers. Nevertheless, for
simplification, statistical analysis considered the two groups
as one (NDC).
Tab l e 1summarizes mean age, MMSE, as well as CSF
total tau, Aβ42, Aβ1–42%, and Aβ1–40ox % levels of the
diagnostic groups.
3.1.1. Neurochemical Phenotype of AD versus NDC. AD was
characterized by decreased values of Aβ42 (P=1.8×10−10)
and Aβ1–42% (P=2.8×10−15).In contrast, tau (P=4.8×
10−10)andAβ1–40ox %(P=1.1×10−2)wereelevatedinAD.
3.1.2. Neurochemical Phenotype of DLB versus NDC. DLB
patients showed lower levels of Aβ42 (P=3.3×10−6)
and Aβ1–42% (P=2.3×10−5), but higher Aβ1–40ox %
concentrations than NDC (P=9.0×10−6).Tau l e ve ls ten d e d
to be increased, but failed the level of significance.
3.1.3. Neurochemical Phenotype of PDD versus NDC. PDD
patients showed lower levels of Aβ42 (P=1.4×10−4)and
Aβ1–42%(P =1×10−5) than NDC. Aβ1–40ox% was elevated
in PDD (P =1.7×10−2).Tau was unchanged between PDD
and NDC.
3.1.4. Neurochemical Phenotype of AD versus DLB and PDD.
AD displayed lower Aβ1–42% levels than DLB (P=5.9×
10−7)andPDD(P=4.2×10−7).Aβ42 levels did not
significantly differ from DLB and PDD. Aβ1–40ox%was
lowered in DLB (P=2.6×10−6), but did not significantly
differfromPDD.TaulevelswereelevatedinADascompared
to DLB (P=2.8×10−3)andPDD(P=7.1×10−5),
respectively.
3.1.5. Neurochemical Phenotype of DLB versus PDD. The
main differences were elevated levels of Aβ1–40ox%inDLB
(P=1.3×10−3).Aβ42 was lower in DLB (P=3.0×10−2),
whereas Aβ1–42% and tau were not significantly altered
among the two groups.
3.2. Correlations. Analysis of each diagnostic group gave
the following significant correlations. In NDC, Aβ42 and
Aβ1–42% were positively correlated to each other. Higher
values of Aβ1–40ox%werecorrelatedwithmalesex.Negative
correlations were observed between Aβ1–42% and age as well
as Aβ1–40ox% and MMSE score. In AD, Aβ42 was positively
correlated with Aβ1–42% and male sex, respectively. In PDD,
Aβ42 was positively correlated with Aβ1–42%, but negatively
with tau levels. No significant correlations were observed in
the DLB group.
3.3. Estimates. The results of ROC analysis for each relevant
differential diagnostic testing are summarized in Table 2.
Figures 1–3show Receiver operator curves for the most
relevant differential diagnostic testings.
4. Discussion
4.1. Biomarker Patterns in the Different Dementia Groups.
In agreement with numerous previous studies, we found
high levels of tau accompanied by low CSF Aβ42 levels in
AD in contrast to nondemented disease controls [2,13].
In DLB and PDD, these biomarkers displayed a rather
unspecific pattern: tau proteins have been found to be in

4 International Journal of Alzheimer’s Disease
Tab l e 2: Cutoffpoints, sensitivities, and specificities.
differential diagnosis Parameter cut offsensitivity specificity Youden index AUC 95%-CI
AD versus DLB
Aβ42/tau 1.163 80% 53% 0.33 0.664 0.483–0.845
Aβ1–42% 5.093 80% 100% 0.80 0.933 0.872–0.994
Aβ1–40ox% 1.144 89% 87% 0.76 0.908 0.802–1.014
AD versus PDD
Aβ42/tau 1.450 91% 67% 0.58 0.775 0.630–0.919
Aβ1–42% 5.730 93% 86% 0.79 0.889 0.773–1.005
Aβ1–40ox% 1.104 87% 43% 0.30 0.592 0.420–0.763
AD versus DLB and PDD
Aβ42/tau 1.450 91% 56% 0.47 0.728 0.610–0.747
Aβ1–42% 5.093 80% 92% 0.72 0.907 0.834–0.981
Aβ1–40ox% 1.104 87% 61% 0.48 0.723 0.600–0.847
DLB versus PDD
Aβ42/tau 3.229 93% 43% 0.36 0.663 0.487–0.840
Aβ1–42% 8.855 80% 33% 0.13 0.597 0.395–0.799
Aβ1–40ox% 1.244 80% 71% 0.51 0.810 0.667–0.952
DLB versus AD and PDD
Aβ42/tau 0.546 80% 26% 0.06 0.560 0.396–0.723
Aβ1–42% 5.198 87% 61% 0.59 0.765 0.658–0.871
Aβ1–40ox% 1.144 87% 80% 0.67 0.877 0.769–0.985
0 0.2 0.4 0.6 0.8 1
1
0.8
0.6
0.4
0.2
0
Aβ42/tau Reference line
Sensitivity
Aβ1–42%
1-specificity
Aβ1–40ox%
Figure 1: Receiver operator curves for detection of AD among DLB
and PDD as a combined group using Aβ42/tau, Aβ1–42% and Aβ1–
40ox%, respectively.
a normal range or slightly increased, paralleled by mildly to
moderately decreased CSF Aβ1–42 levels [14–19]. Rises of
CSF tau levels have also been detected in Creutzfeldt-Jakob
Disease (CJD), vascular dementias and after acute stroke
[13,20,21], indicating tau to be a sensitive biomarker for
neurodestruction, but unspecific for the underlying disease
process. The range of results for tau levels in DLB and
PDD may result from some unexpected variance of values
depending on the actual dynamic of neuronal decay at the
time of lumbar puncture. Moreover, clinical diagnosis of
DLB and PDD may be confounded with AD and vice versa.
The selection of control groups varies among the different
studies. In the present study, we compare dementia groups to
0 0.2 0.4 0.6 0.8 1
1
0.8
0.6
0.4
0.2
0
Aβ42/tau Reference line
Sensitivity
Aβ1–40ox%Aβ1–42%
1-specificity
Figure 2: Receiver operator curves for detection of DLB among AD
and PDD as a combined group using Aβ42/tau, Aβ1–42% and Aβ1–
40ox%, respectively.
diseased controls that include neurodegenerative disorders,
like Parkinson’s disease. This may lead to a higher overlap
of CSF tau values than in studies in which healthy controls
served for comparison. Especially, when taking into account
that PDD may be considered as a clinical state of Parkinson’s
disease.
The decrease of raw CSF Aβ42 concentrations can also be
found in dementias other than AD, but then often in the wake
of an overall drop of CSF Aβpeptides [3,4]. In contrast, the
selective decrease of the Aβ1–42 concentration as compared
to constant Aβ-overall concentrations is more specific for
AD [3]. In line with previous results, the diagnostic accuracy
between AD and other dementias could be clearly improved

International Journal of Alzheimer’s Disease 5
0 0.2 0.4 0.6 0.8 1
1
0.8
0.6
0.4
0.2
0
Aβ42/tau Reference line
Sensitivity
Aβ1–40ox%Aβ1–42%
1-specificity
Figure 3: Receiver operator curves for differentiating DLB from
PDD using Aβ42/tau, Aβ1–42% and Aβ1–40ox%, respectively.
by scaling Aβ42 as a percentage portion of the sum of all
investigated Aβpeptides (Aβ1–42%) [3].
Regarding Aβ1–40ox%,thepresentstudyconfirmsour
previous results of its elevated CSF levels in DLB [4].
Remarkably, Aβ1–40ox% was only mildly elevated in AD
and PDD as compared to controls, leading to a considerably
smaller area of overlapping values in comparison to DLB.
4.2. Diagnostic Accuracies for AD and DLB Using Aβ42/Tau,
Aβ1–42%and, Aβ1–40ox%,Respectively.According to the
references of The Working Group on “Molecular and Bio-
chemical Markers of Alzheimer’s Disease” [22], reasonable
diagnostic accuracies of the tau/Aβ1–42 ratio have been
reported for detecting AD among nondemented, either
healthy or diseased controls [23]. The specificity of this
marker combination declined considerably down to 58%
when differentiating AD from other neurodegenerative
dementias, due to a large overlap of values [9]. We found
similar results in the present study. In contrast, disease
specific changes of CSF AβpeptidepatternsinADandDLB
enabled higher accuracies for their differential diagnosis,
also in discrimination to PDD. With accuracies of 80%
at minimum, low CSF levels of Aβ1–42% were the most
accurate biomarker for diagnosing AD among PDD alone
and in a combined group of DLB and PDD. For the
differentiation of AD from DLB, Aβ1–42% and Aβ1–40ox%
yielded comparable accuracies of 80% at minimum. The
differential diagnosis of DLB and PDD could be made at a
sensitivity and specificity of 80% and 71%, respectively, using
Aβ1–40ox% as the most accurate biomarker. These accuracies
fall within the range of the aforementioned requirements or
come close to it [22].
The reason for relative Aβpeptide values being superior
to raw Aβlevels include: (i) Aβ1–42, but not Aβ1–40/Aβ1–
42 showed a U-shaped natural course in normal aging
[24]; (ii) in contrast to absolute Aβpeptide values, the
relative abundances remained largely stable after different
preanalytical procedures [11,25]; (iii) referencing Aβ1–42
to Aβ1–40 avoids false positive and negative AD diagnosis
in patients with constitutionally low and high CSF Aβ42
levels, respectively [26];and(iv)dementiaswithlowAβ42
levels in the course of an overall decrease of CSF Aβpeptides
will be sorted out from the diagnosis of AD [3]. The
whole amount of CSF Aβpeptides measurable in the Aβ-
SDS-PAGE/immunoblot is closely correlated to CSF Aβ1–
40 levels [26]. This makes it possible to insert the ratio
Aβ1–42/Aβ1–40 as a substitute for Aβ1–42%. Thus, the
above considerations apply to both Aβpeptide ratios and
percentage Aβpeptide values.
4.3. Conclusions. We consider CSF Aβ42/tau to be a sensitive
biomarker for detection of AD, but not specific enough
for excluding other forms of dementia, like DLB and PDD.
Yielding contrasts of 80% or greater, decreased CSF Aβ1–
42% and elevated Aβ1–40ox% are promising biomarker
candidates for AD and DLB, respectively. However, the
pathophysiological meaning of these biomarkers in the
development of AD and DLB remains to be clarified.
ThefurtherprogressofAβ-peptide patterns as applicable
biomarkers requires validation in independent studies on
neuropathologically confirmed cases. Under this respect, we
recently showed that Aβ1–40ox%doesnotdiffer among
clinically and neuropathologically defined cases of DLB
[27]. The major component of Lewy bodies, α-synuclein,
displayed reduced CSF levels in Parkinson’s disease and
DLB as compared to AD and controls [28,29]. For future
studies on differentially diagnosing DLB, we propose the
investigation of combined CSF α-synuclein and Aβ1–40ox%
levels. Furthermore, there is a need for translating the mea-
surement of Aβ1–42% and Aβ1–40ox% into more common
assay formats, like ELISA [30].
4.4. Limitations of the Study. Our results are limited by the
reliance on clinical diagnosis results, because of potential
misclassification. Another point of concern is the size of
patient groups for DLB and PDD.
Abbreviations
Aβpeptides: amyloid-beta peptides
Aβ-SDS-PAGE/immunoblot: amyloid-beta-sodium-
dodecyl-sulphate-
polyacrylamide-gel
electrophoresis with western
immunoblot
AD: Alzheimer’s disease
CCD-camera: charge coupled device
camera
CSF: cerebrospinal fluid
DLB: dementia with Lewy bodies
ECL: enhanced
chemiluminescence
ELISA: Enzyme Linked
Immunosorbent Assay

6 International Journal of Alzheimer’s Disease
MMSE: Mini-Mental-Status
Examination
NINCDS-ADRDA: National Institute of
Neurological and
Communicative Disorders
and Stroke-Alzheimer’s
Disease and Related
Disorders Association
NDC: nondemented disease
controls
PDD: Parkinson’s disease dementia
SDS: sodium dodecyl sulphate.
Acknowledgments
This study was supported by the following Grants: EU
Grants cNEUPRO (Contract no. LSHM-CT-2007-037950),
and neuroTAS (Contract no. LSHB-CT-2006-037953). The
authors would like to thank Sabine Lehmann, Birgit Otte,
and Heike Zech for excellent technical assistance.
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