Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease.
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.
Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research, Ulm University, Ulm, Germany.
M
M
Watabe-Rudolph
Z
Z
Song
L
L
Lausser
C
C
Schnack
Y
Y
Begus-Nahrmann
M-O
MO
Scheithauer
G
G
Rettinger
M
M
Otto
H
H
Tumani
D R
DR
Thal
J
J
Attems
K A
KA
Jellinger
H A
HA
Kestler
C A F
CA
von Arnim
K L
KL
Rudolph
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000201:enzymology*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002688:Chitinases / Q000134:cerebrospinal fluid*; D004249:DNA Damage / Q000502:physiology; D003704:Dementia / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000201:enzymology; D003937:Diagnosis, Differential; D005260:Female; D006596:Hexosaminidases / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D008875:Middle Aged; D020648:Peptide Elongation Factor 1 / Q000134:cerebrospinal fluid; D050777:Stathmin / Q000134:cerebrospinal fluid; D016615:Telomere / Q000502:physiology
D015415:Biomarkers; D020648:Peptide Elongation Factor 1; D050777:Stathmin; D006596:Hexosaminidases; D002688:Chitinases