Cited by 2,065Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCerebrospinal fluid and hydrocephalus

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Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects

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Shaw, Leslie M., Vanderstichele, Hugo, Knapik‐Czajka, 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., Alzheimer's Disease Neuroimaging Initiative·2009·Annals of Neurology

DOI 10.1002/ana.21610PMC PMC2696350

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Abstract

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

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Authors: Shaw, L. M., Vanderstichele, H., Knapik‐Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., Blennow, K., Soares, H., Simon, A., Lewczuk, P., Dean, R., Siemers, E., Potter, W., Lee, V. M. ‐., Trojanowski, J. Q., & Initiative, A. D. N.
Affiliations: University of Pennsylvania (US)
Fujirebio (Belgium) (BE)
University of California San Diego (US)
Mayo Clinic (US)
University of Gothenburg (SE)
Pfizer (United States) (US)
Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
Eli Lilly (United States) (US)
Corresponding author: Shaw, Leslie M.
ORCID: Shaw, Leslie M.
Clark, Christopher M.
Petersen, Ronald C.
Blennow, Kaj
Soares, Holly
Lewczuk, Piotr
Siemers, Eric
Lee, Virginia M.‐Y.
Trojanowski, John Q.
Venue: Annals of Neurology
Publisher: Wiley
Published: 2009-04
Volume: 65
Issue: 4
Pages: 403-413
ISSN: 0364-5134 (ISSN-L)
1531-8249
DOI: 10.1002/ana.21610
PMC: PMC2696350
OpenAlex: W2008301592
Cited by: 2,065
References: 31
Citations by year: 2026: 59 · 2025: 82 · 2024: 110 · 2023: 89 · 2022: 114 · 2021: 125 · 2020: 136 · 2019: 141 · 2018: 129 · 2017: 135 · 2016: 121 · 2015: 146 · 2014: 131 · 2013: 130 · 2012: 136
FWCI: 85.14
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Annals of Neurology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: University of Pennsylvania
National Institutes of Health (5u01ag024904-10)
National Institute on Aging (U01-AG-024904, AG 024904, P30AG010124, AG-10124, U19AG010483, U19AG024904)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
Keywords: Alzheimer's disease, cerebrospinal fluid biomarkers, amyloid-beta 42, total tau, mild cognitive impairment, conversion to Alzheimer's disease, APOE ε4, Alzheimer's Disease Neuroimaging Initiative
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Diagnostic Imaging, Female, Humans, Male, Middle Aged, Peptide Fragments, Phosphorylation, Retrospective Studies, ROC Curve, Sensitivity and Specificity, Threonine, Cohort Studies, Biomarkers, Amyloid beta-Peptides, tau Proteins, Disease Progression, Statistics, Nonparametric, Area Under Curve, Apolipoprotein E4

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Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects

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