Journal
NEUROLOGY
Volume 78, Issue 8, Pages 569-577Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1212/WNL.0b013e318247caa1
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [KFO 142: RU745-13]
- European Union (Geninca, Telomarker)
- Academy of Sciences and Humanities, Heidelberg (WIN-Kolleg)
- Bundesministerium fur Bildung und Forschung (BMBF)
- European Commission (NaDiNe)
- Bayer Schering Pharma
- Biogen Idec
- Genzyme Corp.-Virotec
- Merck Serono
- Novartis
- Roche
- Teva Pharmaceutical Industries Ltd.
- Gemeinnutzige Hertie-Stiftung
- GBS-Polyradiculitis-Stiftung
- University of Ulm
- Landesstiftung BW
- Alzheimer Forschung Initiative
- Biomedical Research Centre (UK)
- Alzheimer Research UK
- Dunhill Medical Trust
- Society for Support of Research in Experimental Neurology, Vienna, Austria
- German Science Foundation (DFG)
- German federal ministry of education and research (BMBF)
- sanofi-aventis
- Pfizer Inc
- Eisai Inc.
- Nutricia GmbH
- Heel GmbH
- Heidelberg Academy of Science and the Humanities
- Medical Research Council [G0502157, G0400074, G0700718B, G1100540, G0900652] Funding Source: researchfish
- MRC [G1100540, G0400074, G0502157, G0900652] Funding Source: UKRI
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Objective: DNA damage accumulation in brain is associated with the development of Alzheimer disease (AD), but newly identified protein markers of DNA damage have not been evaluated in the diagnosis of AD and other forms of dementia. Methods: Here, we analyzed the level of novel biomarkers of DNA damage and telomere dysfunction (chitinase activity, N-acetyl-glucosaminidase activity, stathmin, and EF-1 alpha) in CSF of 94 patients with AD, 41 patients with non-AD dementia, and 40 control patients without dementia. Results: Enzymatic activity of chitinase (chitotriosidase activity) and stathmin protein level were significantly increased in CSF of patients with AD and non-AD dementia compared with that of no dementia control patients. As a single marker, chitinase activity was most powerful for distinguishing patients with AD from no dementia patients with an accuracy of 85.8% using a single threshold. Discrimination was even superior to clinically standard CSF markers that showed an accuracy of 78.4% (beta-amyloid) and 77.6% (tau). Combined analysis of chitinase with other markers increased the accuracy to a maximum of 91%. The biomarkers of DNA damage were also increased in CSF of patients with non-AD dementia compared with no dementia patients, and the new biomarkers improved the diagnosis of non-AD dementia as well as the discrimination of AD from non-AD dementia. Conclusions: Taken together, the findings in this study provide experimental evidence that DNA damage markers are significantly increased in AD and non-AD dementia. The biomarkers identified outperformed the standard CSF markers for diagnosing AD and non-AD dementia in the cohort investigated. Neurology (R) 2012;78:569-577
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