AAN.com
Quick search in Citations
AnywhereCitation
Advanced Search
Trending Terms:
Articles
February 8, 2012

Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease

M. Watabe-Rudolph, MD, Z. Song, MD, L. Lausser, MSc, C. Schnack, PhD, Y. Begus-Nahrmann, PhD, M.-O. Scheithauer, MD, G. Rettinger, MD, … Show All … , M. Otto, MD, H. Tumani, MD, D.R. Thal, MD, J. Attems, MD, K.A. Jellinger, MD, H.A. Kestler, PhD, C.A.F. von Arnim, MD, and K.L. Rudolph, MDAuthors Info & Affiliations
February 21, 2012 issue
78 (8) 569-577
https://doi.org/10.1212/WNL.0b013e318247caa1
Letters to the Editor
Track CitationsAdd to favorites
Get Access

Abstract

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-1α) 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% (β-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.

Get full access to this article

View all available purchase options and get full access to this article.

Get Access

Supplementary Material

File (watabe_78_569.pdf)
File (wnl203439-figure_e-1.pdf)
File (wnl203439-figure_e-2.pdf)
File (wnl203439-figure_e-3.pdf)
File (wnl203439-table_e-1.doc)
File (wnl203439-table_e-2.doc)
File (wnl203439-table_e-3.doc)

REFERENCES

1.
Williams R. Biomarkers: warning signs. Nature 2011; 475: S5– S7.
Crossref
PubMed
Google Scholar
2.
Rass U, Ahel I, West SC. Defective DNA repair and neurodegenerative disease. Cell 2007; 130: 991– 1004.
Crossref
PubMed
Google Scholar
3.
Mecocci P, MacGarvey U, Beal MF. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann Neurol 1994; 36:747– 751.
Crossref
PubMed
Google Scholar
4.
Tobi SE, Itzhaki RF. DNA double-strand breaks measured by pulsed-field gel electrophoresis in irradiated lymphocytes from normal humans and those with Alzheimer's disease. Int J Radiat Biol 1993; 63: 617– 622.
Crossref
PubMed
Google Scholar
5.
Myung NH, Zhu X, Kruman II, et al. Evidence of DNA damage in Alzheimer disease: phosphorylation of histone H2AX in astrocytes. Age 2008; 30: 209– 215.
Crossref
PubMed
Google Scholar
6.
Simpson JE, Ince PG, Haynes LJ, et al. Population variation in oxidative stress and astrocyte DNA damage in relation to Alzheimer-type pathology in the ageing brain. Neuropathol Appl Neurobiol 2010; 36: 25– 40.
Crossref
PubMed
Google Scholar
7.
Brasnjevic I, Hof PR, Steinbusch HW, Schmitz C. Accumulation of nuclear DNA damage or neuron loss: molecular basis for a new approach to understanding selective neuronal vulnerability in neurodegenerative diseases. DNA Repair 2008; 7: 1087– 1097.
Crossref
PubMed
Google Scholar
8.
Allsopp RC, Vaziri H, Patterson C, et al. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 1992; 89:10114– 10118.
Crossref
PubMed
Google Scholar
9.
Panossian LA, Porter VR, Valenzuela HF, et al. Telomere shortening in T cells correlates with Alzheimer's disease status. Neurobiol Aging 2003; 24: 77– 84.
Crossref
PubMed
Google Scholar
10.
Lukens JN, Van Deerlin V, Clark CM, Xie SX, Johnson FB. Comparisons of telomere lengths in peripheral blood and cerebellum in Alzheimer's disease. Alzheimers Dement 2009; 5: 463– 469.
Crossref
PubMed
Google Scholar
11.
Thomas P, O'Callaghan NJ, Fenech M. Telomere length in white blood cells, buccal cells and brain tissue and its variation with ageing and Alzheimer's disease. Mech Ageing Dev 2008; 129: 183– 190.
Crossref
PubMed
Google Scholar
12.
Jiang H, Schiffer E, Song Z, et al. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease. Proc Natl Acad Sci USA 2008; 105: 11299– 11304.
Crossref
PubMed
Google Scholar
13.
Reiber H, Otto M, Trendelenburg C, Wormek A. Reporting cerebrospinal fluid data: knowledge base and interpretation software. Clin Chem Lab Med 2001; 39: 324– 332.
Crossref
PubMed
Google Scholar
14.
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 1984; 34: 939– 944.
Crossref
PubMed
Google Scholar
15.
Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998; 51: 1546– 1554.
Crossref
PubMed
Google Scholar
16.
Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies: report of the NINDS-AIREN International Workshop. Neurology 1993; 43: 250– 260.
Crossref
PubMed
Google Scholar
17.
McKeith IG. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the Consortium on DLB International Workshop. J Alzheimers Dis 2006; 9: 417– 423.
Crossref
PubMed
Google Scholar
18.
Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 1996; 47: 1– 9.
Crossref
PubMed
Google Scholar
19.
Emre M. Clinical features, pathophysiology and treatment of dementia associated with Parkinson's disease. Handb Clin Neurol 2007; 83: 401– 419.
Crossref
PubMed
Google Scholar
20.
Brettschneider J, Petzold A, Schottle D, Claus A, Riepe M, Tumani H. The neurofilament heavy chain (NfH) in the cerebrospinal fluid diagnosis of Alzheimer's disease. Dement Geriatr Cogn Disord 2006; 21: 291– 295.
Crossref
PubMed
Google Scholar
21.
Reiber H, Peter JB. Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci 2001; 184: 101– 122.
Crossref
PubMed
Google Scholar
22.
Bossuyt PM, Reitsma JB, Bruns DE, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. Fam Pract 2004; 21:4– 10.
Crossref
PubMed
Google Scholar
23.
Duda RO, Hart, Peter E, Stork, David G. Pattern Classification, 2nd ed. Chichester, UK: Wiley-Interscience; 2001.
Google Scholar
24.
Silverman BW. Density Estimation for Statistics and Data Analysis. London: Chapman and Hall; 1986.
Google Scholar
25.
Cheon MS, Fountoulakis M, Cairns NJ, Dierssen M, Herkner K, Lubec G. Decreased protein levels of stathmin in adult brains with Down syndrome and Alzheimer's disease. J Neural Transm Suppl 2001: 281– 288.
PubMed
Google Scholar
26.
Miyasaka T, Sato S, Tatebayashi Y, Takashima A. Microtubule destruction induces tau liberation and its subsequent phosphorylation. FEBS Lett 2010; 584: 3227– 3232.
Crossref
PubMed
Google Scholar
27.
Bussink AP, Speijer D, Aerts JM, Boot RG. Evolution of mammalian chitinase(-like) members of family 18 glycosyl hydrolases. Genetics 2007; 177: 959– 970.
Crossref
PubMed
Google Scholar
28.
Colton CA, Mott RT, Sharpe H, Xu Q, Van Nostrand WE, Vitek MP. Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD. J Neuroinflammation 2006; 3: 27.
Crossref
PubMed
Google Scholar
29.
Craig-Schapiro R, Perrin RJ, Roe CM, et al. YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer's disease. Biol Psychiatry 2010; 68: 903– 912.
Crossref
PubMed
Google Scholar
30.
Perrin RJ, Craig-Schapiro R, Malone JP, et al. Identification and validation of novel cerebrospinal fluid biomarkers for staging early Alzheimer's disease. PLoS One 2011; 6:e16032.
Crossref
PubMed
Google Scholar
31.
Bonneh-Barkay D, Wang G, Starkey A, Hamilton RL, Wiley CA. In vivo CHI3L1 (YKL-40) expression in astrocytes in acute and chronic neurological diseases. J Neuroinflammation 2010; 7: 34.
Crossref
PubMed
Google Scholar
32.
Di Rosa M, Dell'Ombra N, Zambito AM, Malaguarnera M, Nicoletti F, Malaguarnera L. Chitotriosidase and inflammatory mediator levels in Alzheimer's disease and cerebrovascular dementia. Eur J Neurosci 2006; 23: 2648– 2656.
Crossref
PubMed
Google Scholar
33.
Casal JA, Robles A, Tutor JC. Serum markers of monocyte/macrophage activation in patients with Alzheimer's disease and other types of dementia. Clin Biochem 2003; 36: 553– 556.
Crossref
PubMed
Google Scholar
34.
Mattsson N, Tabatabaei S, Johansson P, et al. Cerebrospinal fluid microglial markers in Alzheimer's disease: elevated chitotriosidase activity but lack of diagnostic utility. Neuromolecular Med 2011; 13: 151– 159.
Crossref
PubMed
Google Scholar
35.
Boden N, Sommer U, Spindler KD. Demonstration and characterization of chitinases in the Drosophila Kc cell line. Insect Biochem 1985; 15: 19– 23.
Crossref
Google Scholar
36.
Castellani RJ, Siedlak SL, Fortino AE, Perry G, Ghetti B, Smith MA. Chitin-like polysaccharides in Alzheimer's disease brains. Curr Alzheimer Res 2005; 2: 419– 423.
Crossref
PubMed
Google Scholar
37.
Malaguarnera L, Ohazuruike LN, Tsianaka C, Antic T, Di Rosa M, Malaguarnera M. Human chitotriosidase polymorphism is associated with human longevity in Mediterranean nonagenarians and centenarians. J Hum Genet 2010; 55: 8– 12.
Crossref
PubMed
Google Scholar
38.
Gasser S, Orsulic S, Brown EJ, Raulet DH. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 2005; 436: 1186– 1190.
Crossref
PubMed
Google Scholar
39.
Tarawneh R, Holtzman DM. Biomarkers in translational research of Alzheimer's disease. Neuropharmacology 2010; 59: 310– 322.
Crossref
PubMed
Google Scholar
40.
Lee JM, Blennow K, Andreasen N, et al. The brain injury biomarker VLP-1 is increased in the cerebrospinal fluid of Alzheimer disease patients. Clin Chem 2008; 54: 1617– 1623.
Crossref
PubMed
Google Scholar

Information & Authors

Information

Published In

Neurology®
Volume 78 • Number 8 • February 21, 2012
Pages: 569-577
PubMed: 22323746

Copyright

Copyright © 2012 by AAN Enterprises, Inc.

Publication History

Received: June 3, 2011
Accepted: September 13, 2011
Published online: February 8, 2012
Published in print: February 21, 2012

Permissions

Request permissions for this article.

Disclosure

Dr. Watabe-Rudolph, Dr. Song, L. Lausser, Dr. Schnack, Dr. Begus-Nahrmann, Dr. Scheithauer, and Dr. Rettinger report no disclosures. Dr. Otto has received research support from the Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), and the European Commission (NaDiNe). Dr. Tumani serves on a scientific advisory board, as a consultant for, or received funding for research projects and travel from Bayer Schering Pharma, Biogen Idec, Genzyme Corp.-Virotec, Merck Serono, Novartis, Roche, and Teva Pharmaceutical Industries Ltd.; serves on the editorial board of MS International; and receives research support from Gemeinnützige Hertie-Stiftung, GBS-Polyradiculitis-Stiftung, University of Ulm, Landesstiftung BW, and Deutsche Forschunggemeinschaft. Dr. Thal serves on the editorial boards of Acta Neuropathologica, Frontiers in Neurodegeneration, and Journal of Neuroinflammation; received a speaker honorarium from Novartis; and receives research support from Novartis, Deutsche Forschungsgemeinschaft (DFG), and the Alzheimer Forschung Initiative. Dr. Attems receives research support from Biomedical Research Centre (UK), Alzheimer Research UK, and Dunhill Medical Trust. Dr. Jellinger serves as senior editor of Acta Neuropathologica and on the editorial boards of numerous journals and receives research support from the Society for Support of Research in Experimental Neurology, Vienna, Austria. Dr. Kestler serves as an Associate Editor of Computational Statistics; receives publishing royalties for Mathe-Toolbox (Lehmanns Media, 2010); and has received research support from the German Science Foundation (DFG) and the German federal ministry of education and research (BMBF). Dr. von Arnim served on a scientific advisory board of Nutricia GmbH; has received funding for travel and speaker honoraria from sanofi-aventis, Novartis, Pfizer Inc, Eisai Inc., and Nutricia GmbH; and receives research support from Heel GmbH, Alzheimer Forschung Initiative, and the Heidelberg Academy of Science and the Humanities. Dr. Rudolph has filed a patent for the use of chitinase activity, n-glucosaminidase activity, EF1α, and stathmin for the analysis of DNA damage accumulation, aging, and age-associated diseases.

Authors

Affiliations & Disclosures

M. Watabe-Rudolph, MD*
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
Z. Song, MD*
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
L. Lausser, MSc*
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
C. Schnack, PhD*
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
Y. Begus-Nahrmann, PhD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
M.-O. Scheithauer, MD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
G. Rettinger, MD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
M. Otto, MD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
H. Tumani, MD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
D.R. Thal, MD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
J. Attems, MD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
K.A. Jellinger, MD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
H.A. Kestler, PhD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
C.A.F. von Arnim, MD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author
K.L. Rudolph, MD
From the Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research (M.W.-R., M.-O.S., G.R.), Department of Stem Cell Aging (Z.S., Y.B.-N., K.L.R.), Department of Neurology (C.S., M.O., H.T., C.A.F.v.A.), Department of Pathology (D.R.T.), and Institute of Neural Information Processing (L.L., H.A.K.), Ulm University, Ulm, Germany; Department of Colorectal Surgery (Z.S.), Sir Run Run Shaw Hospital, Zhenjiang University, Hangzhou, China; Institute for Ageing and Health (J.A.), Newcastle University, Newcastle upon Tyne, UK; and Institute of Clinical Neurobiology (K.J.A.), University of Vienna, Vienna, Austria.
View all articles by this author

Notes

*
These authors contributed equally to this work.
Study funding: Supported by the Deutsche Forschungsgemeinschaft (KFO 142: RU745-13) and the European Union (Geninca, Telomarker) (K.L.R.) and by a grant from the Academy of Sciences and Humanities, Heidelberg (WIN-Kolleg) (C.A.F.v.A.).
Correspondence & reprint requests to Dr. Kestler: [email protected] Dr. von Arnim: [email protected] Dr. Rudolph: [email protected].

Author Contributions

Dr. Watabe-Rudolph, Dr. Song, L. Lausser, Dr. Schnack: analysis and interpretation of data, acquisition of data, manuscript revision. Dr. Begus-Nahrmann, Dr. Rettinger, Dr. Otto, Dr. Tumani, Dr. Thal: manuscript preparation, acquisition of data. Dr. Attems, Dr. Jellinger: manuscript preparation, histologic analysis of postmortem biopsies. L. Lausser, Dr. Kestler: statistical analysis. Dr. Kestler, Dr. von Arnim, Dr. Rudolph: manuscript drafting and revision, study concept and design, analysis and interpretation of data, acquisition of data, study supervision and coordination.

Metrics & Citations

Metrics

Citation information is sourced from Crossref Cited-by service.

Citations

Download Citations

If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Select your manager software from the list below and click Download.

Cited By
    • Dietmar Rudolf Thal,
    • Koen Poesen,
    • Rik Vandenberghe,
    • Steffi De Meyer,
    Alzheimer's disease neuropathology and its estimation with fluid and imaging biomarkers, Molecular Neurodegeneration, 20, 1, (2025).https://doi.org/10.1186/s13024-025-00819-y
    Crossref
    • Wenkai Yang,
    • Weihua Yu,
    • Yang Lv,
    Neuroprotective effects of chitinase-1 and calcitonin gene-related peptide on Alzheimer's disease by promoting lysosomal function, Journal of Alzheimer’s Disease, 103, 3, (879-888), (2025).https://doi.org/10.1177/13872877241307257
    Crossref
    • Charles L. Greenblatt,
    • Richard Lathe,
    Vaccines and Dementia: Part II. Efficacy of BCG and Other Vaccines Against Dementia, Journal of Alzheimer's Disease, 98, 2, (361-372), (2024).https://doi.org/10.3233/JAD-231323
    Crossref
    • Tanvir Ahmed,
    Lipid nanoparticle mediated small interfering RNA delivery as a potential therapy for Alzheimer's disease, European Journal of Neuroscience, 59, 11, (2915-2954), (2024).https://doi.org/10.1111/ejn.16336
    Crossref
    • Ji Eun Yu,
    • In Jun Yeo,
    • Sang-Bae Han,
    • Jaesuk Yun,
    • Bongcheol Kim,
    • Yoon Ji Yong,
    • Young-soo Lim,
    • Tae Hun Kim,
    • Dong Ju Son,
    • Jin Tae Hong,
    Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer, Experimental & Molecular Medicine, 56, 1, (1-18), (2024).https://doi.org/10.1038/s12276-023-01131-9
    Crossref
    • Fardin Nabizadeh,
    Brain white matter damage biomarkers, , (2024).https://doi.org/10.1016/bs.acc.2024.11.005
    Crossref
    • Cristina Russo,
    • Maria Stella Valle,
    • Antonino Casabona,
    • Lucia Malaguarnera,
    Chitinase Signature in the Plasticity of Neurodegenerative Diseases, International Journal of Molecular Sciences, 24, 7, (6301), (2023).https://doi.org/10.3390/ijms24076301
    Crossref
    • Richard Lathe,
    • David St. Clair,
    Programmed ageing: decline of stem cell renewal, immunosenescence, and Alzheimer's disease, Biological Reviews, 98, 4, (1424-1458), (2023).https://doi.org/10.1111/brv.12959
    Crossref
    • Yujun Kim,
    • Hui Li,
    • Joohee Choi,
    • Jihyeon Boo,
    • Hyemi Jo,
    • Ji Young Hyun,
    • Injae Shin,
    Glycosidase-targeting small molecules for biological and therapeutic applications, Chemical Society Reviews, 52, 20, (7036-7070), (2023).https://doi.org/10.1039/D3CS00032J
    Crossref
    • Kazuaki Okawa,
    • Eri Tabata,
    • Yuta Kida,
    • Kyohei Uno,
    • Hidetoshi Suzuki,
    • Minori Kamaya,
    • Peter O. Bauer,
    • Fumitaka Oyama,
    Irreversible evolutionary loss of chitin‐degrading ability in the chitinase‐like protein Y m1 under positive selection in rodents , Protein Science, 32, 4, (2023).https://doi.org/10.1002/pro.4620
    Crossref
  11. See more

View Options

Login options

Check if you have access through your login credentials or your institution to get full access on this article.

Personal login Institutional Login
Purchase Options

The neurology.org payment platform is currently offline. Our technical team is working as quickly as possible to restore service.

If you need immediate support or to place an order, please call or email customer service:

  • 1-800-638-3030 for U.S. customers - 8:30 - 7 pm ET (M-F)
  • 1-301-223-2300 for customers outside the U.S. - 8:30 - 7 pm ET (M-F)
  • [email protected]

We appreciate your patience during this time and apologize for any inconvenience.

View options

PDF and All Supplements

Download PDF and Supplementary Material

Full Text

View Full Text

Full Text HTML

View Full Text HTML

Figures

Tables

Media

Share

Share

Share article link

Share

View full text|Download PDF