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Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects.
Ann Neurol 2009; 65(4):403-13AN

Abstract

OBJECTIVE

Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects.

METHODS

Amyloid-beta 1 to 42 peptide (A beta(1-42)), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy-confirmed AD cases and 52 age-matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t-tau and A beta(1-42) in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy-confirmed CSF data.

RESULTS

CSF A beta(1-42) was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for A beta(1-42), t-tau, and APO epsilon 4 allele count provided the best assessment delineation of mild AD. An AD-like baseline CSF profile for t-tau/A beta(1-42) was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study.

INTERPRETATION

The CSF biomarker signature of AD defined by A beta(1-42) and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, Institute on Aging, Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. shawlmj@mail.med.upenn.edu

Pub Type(s)

Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

19296504

Citation

Shaw, Leslie M., et al. "Cerebrospinal Fluid Biomarker Signature in Alzheimer's Disease Neuroimaging Initiative Subjects." Annals of Neurology, vol. 65, no. 4, 2009, pp. 403-13.
Shaw LM, Vanderstichele H, Knapik-Czajka M, et al. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Ann Neurol. 2009;65(4):403-13.
Shaw, L. M., Vanderstichele, H., Knapik-Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., ... Trojanowski, J. Q. (2009). Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Annals of Neurology, 65(4), pp. 403-13. doi:10.1002/ana.21610.
Shaw LM, et al. Cerebrospinal Fluid Biomarker Signature in Alzheimer's Disease Neuroimaging Initiative Subjects. Ann Neurol. 2009;65(4):403-13. PubMed PMID: 19296504.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. AU - Shaw,Leslie M, AU - Vanderstichele,Hugo, AU - Knapik-Czajka,Malgorzata, AU - Clark,Christopher M, AU - Aisen,Paul S, AU - Petersen,Ronald C, AU - Blennow,Kaj, AU - Soares,Holly, AU - Simon,Adam, AU - Lewczuk,Piotr, AU - Dean,Robert, AU - Siemers,Eric, AU - Potter,William, AU - Lee,Virginia M-Y, AU - Trojanowski,John Q, AU - ,, PY - 2009/3/20/entrez PY - 2009/3/20/pubmed PY - 2009/5/20/medline SP - 403 EP - 13 JF - Annals of neurology JO - Ann. Neurol. VL - 65 IS - 4 N2 - OBJECTIVE: Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. METHODS: Amyloid-beta 1 to 42 peptide (A beta(1-42)), total tau (t-tau), and tau phosphorylated at the threonine 181 were measured in (1) cerebrospinal fluid (CSF) samples obtained during baseline evaluation of 100 mild AD, 196 mild cognitive impairment, and 114 elderly cognitively normal (NC) subjects in ADNI; and (2) independent 56 autopsy-confirmed AD cases and 52 age-matched elderly NCs using a multiplex immunoassay. Detection of an AD CSF profile for t-tau and A beta(1-42) in ADNI subjects was achieved using receiver operating characteristic cut points and logistic regression models derived from the autopsy-confirmed CSF data. RESULTS: CSF A beta(1-42) was the most sensitive biomarker for AD in the autopsy cohort of CSF samples: receiver operating characteristic area under the curve of 0.913 and sensitivity for AD detection of 96.4%. In the ADNI cohort, a logistic regression model for A beta(1-42), t-tau, and APO epsilon 4 allele count provided the best assessment delineation of mild AD. An AD-like baseline CSF profile for t-tau/A beta(1-42) was detected in 33 of 37 ADNI mild cognitive impairment subjects who converted to probable AD during the first year of the study. INTERPRETATION: The CSF biomarker signature of AD defined by A beta(1-42) and t-tau in the autopsy-confirmed AD cohort and confirmed in the cohort followed in ADNI for 12 months detects mild AD in a large, multisite, prospective clinical investigation, and this signature appears to predict conversion from mild cognitive impairment to AD. SN - 1531-8249 UR - https://www.unboundmedicine.com/medline/citation/19296504/Cerebrospinal_fluid_biomarker_signature_in_Alzheimer's_disease_neuroimaging_initiative_subjects_ L2 - https://doi.org/10.1002/ana.21610 DB - PRIME DP - Unbound Medicine ER -