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Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Author(s) -
Shaw Leslie M.,
Vanderstichele Hugo,
KnapikCzajka Malgorzata,
Clark Christopher M.,
Aisen Paul S.,
Petersen Ronald C.,
Blennow Kaj,
Soares Holly,
Simon Adam,
Lewczuk Piotr,
Dean Robert,
Siemers Eric,
Potter William,
Lee Virginia M.Y.,
Trojanowski John Q.
Publication year - 2009
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.21610
Subject(s) - biomarker , cerebrospinal fluid , cohort , medicine , receiver operating characteristic , alzheimer's disease , logistic regression , neuroimaging , oncology , autopsy , area under the curve , pathology , alzheimer's disease neuroimaging initiative , gastroenterology , disease , psychiatry , chemistry , biochemistry
Objective Develop a cerebrospinal fluid biomarker signature for mild Alzheimer's disease (AD) in Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects. Methods Amyloid‐β 1 to 42 peptide (Aβ 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 Aβ 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 Aβ 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 Aβ 1–42 , t‐tau, and APO ε 4 allele count provided the best assessment delineation of mild AD. An AD‐like baseline CSF profile for t‐tau/Aβ 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 Aβ 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. Ann Neurol 2009