Brain Advance Access published online on April 6, 2006
Brain, doi:10.1093/brain/awl063
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1 Department of Psychiatry, University of Goettingen, Goettingen, Germany
* To whom correspondence should be addressed. As the differential diagnosis of dementias based on established clinical criteria is often difficult, biomarkers for applicable diagnostic testing are currently under intensive investigation. Amyloid plaques deposited in the brain of patients suffering from Alzheimer's disease, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) mainly consist of carboxy-terminally elongated forms of amyloid-beta (A
Received March 30, 2005
Revised February 14, 2006
Accepted February 20, 2006
Article
CSF amyloid-
Mirko Bibl 1 *,
Brit Mollenhauer 2 *,
Hermann Esselmann 3,
Piotr Lewczuk 3,
Hans-Wolfgang Klafki 3,
Katrin Sparbier 4,
Alexandr Smirnov 5,
Lukas Cepek 6,
Claudia Trenkwalder 5,
Eckart Rüther 1,
Johannes Kornhuber 3,
Markus Otto 6,
and
Jens Wiltfang 3 *
-peptides in Alzheimer's disease, dementia with Lewy bodies and Parkinson's disease dementia
2 Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
3 Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany
4 Bruker Daltronics, Leipzig, Germany
5 Paracelsus-Elena Klinik, Kassel, Germany
6 Department of Neurology, University of Ulm, Steinhövelstr, Ulm, Germany
Jens Wiltfang, E-mail: Jens.Wiltfang{at}psych.imed.uni-erlangen.de
Abstract 
) peptides, such as A1-42. Absolute A1-42 levels in CSF have shown diagnostic value for the diagnosis of Alzheimer's disease, but the discrimination among Alzheimer's disease, DLB and PDD was poor. A recently established quantitative urea-based A-sodium-dodecylsulphate-polyacrylamide-gel-electrophoresis with Western immunoblot (A-SDS-PAGE/immunoblot) revealed a highly conserved A peptide pattern of the carboxy-terminally truncated A peptides 1-37, 1-38, 1-39 in addition to 1-40 and 1-42 in human CSF. We used the A-SDS-PAGE/immunoblot to investigate the CSF of 23 patients with Alzheimer's disease, 21 with DLB, 21 with PDD and 23 non-demented disease controls (NDC) for disease-specific alterations of the A peptide patterns in its absolute and relative quantities. The diagnostic groups were matched for age and severity of dementia. The present study is the first attempt to evaluate the meaning of A peptide patterns in CSF for differential diagnosis of the three neurodegenerative diseases--Alzheimer's disease, DLB and PDD. The A peptide patterns displayed disease-specific variations and the ratio of the differentially altered A1-42 to the A1-37 levels subsequently discriminated all diagnostic groups from each other at a highly significant level, except DLB from PDD. Additionally, a novel peptide with A-like immunoreactivity was observed constantly in the CSF of all 88 investigated patients. The pronounced percentage increase of this peptide in DLB allowed a highly significant discrimination from PDD. Using a cut-off point of 0.954%, this marker yielded a diagnostic sensitivity and specificity of 81 and 71%, respectively. From several lines of indication, we consider this peptide to represent an oxidized 
-helical form of A1-40 (A1-40*). The increased abundance of A1-40* probably reflects a disease-specific alteration of the A1-40 metabolism in DLB. We conclude that A peptide patterns reflect disease-specific pathophysiological pathways of different dementia syndromes as distinct neurochemical phenotypes. Although A peptide patterns failed to fulfil the requirements for a sole biomarker, their combined evaluation with other biomarkers is promising in neurochemical dementia diagnosis. It is noteworthy that DLB and PDD exhibit distinct clinical temporal courses, despite their similar neuropathological appearance. Their distinct molecular phenotypes support the view of different pathophysiological pathways for each of these neurodegenerative diseases. peptides.
*These authors contributed equally to this work.
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