Brain amyloidosis ascertainment from cognitive, imaging, and peripheral blood protein measures
Citation Manager Formats
Make Comment
See Comments

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
Abstract
Background: The goal of this study was to identify a clinical biomarker signature of brain amyloidosis in the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) mild cognitive impairment (MCI) cohort.
Methods: We developed a multimodal biomarker classifier for predicting brain amyloidosis using cognitive, imaging, and peripheral blood protein ADNI1 MCI data. We used CSF β-amyloid 1–42 (Aβ42) ≤192 pg/mL as proxy measure for Pittsburgh compound B (PiB)-PET standard uptake value ratio ≥1.5. We trained our classifier in the subcohort with CSF Aβ42 but no PiB-PET data and tested its performance in the subcohort with PiB-PET but no CSF Aβ42 data. We also examined the utility of our biomarker signature for predicting disease progression from MCI to Alzheimer dementia.
Results: The CSF training classifier selected Mini-Mental State Examination, Trails B, Auditory Verbal Learning Test delayed recall, education, APOE genotype, interleukin 6 receptor, clusterin, and ApoE protein, and achieved leave-one-out accuracy of 85% (area under the curve [AUC] = 0.8). The PiB testing classifier achieved an AUC of 0.72, and when classifier self-tuning was allowed, AUC = 0.74. The 36-month disease-progression classifier achieved AUC = 0.75 and accuracy = 71%.
Conclusions: Automated classifiers based on cognitive and peripheral blood protein variables can identify the presence of brain amyloidosis with a modest level of accuracy. Such methods could have implications for clinical trial design and enrollment in the near future.
Classification of evidence: This study provides Class II evidence that a classification algorithm based on cognitive, imaging, and peripheral blood protein measures identifies patients with brain amyloid on PiB-PET with moderate accuracy (sensitivity 68%, specificity 78%).
GLOSSARY
- Aβ42=
- β-amyloid 1–42;
- AD=
- Alzheimer dementia;
- ADNI1=
- Alzheimer's Disease Neuroimaging Initiative 1;
- AUC=
- area under the curve;
- AVLT=
- Auditory Verbal Learning Test;
- BDNF=
- brain-derived neurotrophic factor;
- CI=
- confidence interval;
- IL-6R=
- interleukin 6 receptor;
- IL-13=
- interleukin 13;
- LOOCV=
- leave-one-out cross-validation;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- NPV=
- negative predictive value;
- PiB=
- Pittsburgh compound B;
- PPV=
- positive predictive value;
- ROC=
- receiver operating characteristic;
- ROI=
- region of interest;
- SUVR=
- standard uptake value ratio;
- SVM=
- support vector machine;
- TNF-α=
- tumor necrosis factor α
Footnotes
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The ADNI investigators contributed to the design and implementation of ADNI and/or provided data. The ADNI investigators list is available on the Neurology® Web site at Neurology.org.
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at Neurology.org
- Received May 21, 2014.
- Accepted in final form October 15, 2014.
- © 2015 American Academy of Neurology
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
For assistance, please contact:
AAN Members (800) 879-1960 or (612) 928-6000 (International)
Non-AAN Member subscribers (800) 638-3030 or (301) 223-2300 option 3, select 1 (international)
Sign Up
Information on how to subscribe to Neurology and Neurology: Clinical Practice can be found here
Purchase
Individual access to articles is available through the Add to Cart option on the article page. Access for 1 day (from the computer you are currently using) is US$ 39.00. Pay-per-view content is for the use of the payee only, and content may not be further distributed by print or electronic means. The payee may view, download, and/or print the article for his/her personal, scholarly, research, and educational use. Distributing copies (electronic or otherwise) of the article is not allowed.
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Dr. Sevil Yaşar and Dr. Behnam Sabayan
► Watch
Topics Discussed
Alert Me
Recommended articles
-
Research Article
Temporal Correlation of CSF and Neuroimaging in the Amyloid-Tau-Neurodegeneration Model of Alzheimer DiseaseAnna H. Boerwinkle, Julie K. Wisch, Charles D. Chen et al.Neurology, April 30, 2021 -
Articles
Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriersMichael Schöll, Anders Wall, Steinunn Thordardottir et al.Neurology, June 13, 2012 -
Article
Alzheimer risk genes modulate the relationship between plasma apoE and cortical PiB bindingAndreas Lazaris, Kristy S. Hwang, Naira Goukasian et al.Neurology Genetics, October 15, 2015 -
Articles
Plasma Aβ and PET PiB binding are inversely related in mild cognitive impairmentD.P. Devanand, N. Schupf, Y. Stern et al.Neurology, June 29, 2011