Low PiB PET retention in presence of pathologic CSF biomarkers in Arctic APP mutation carriers
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
Objective: To investigate the particular pathology of the Arctic APP (APParc) early-onset familial Alzheimer disease (eoFAD) mutation for the first time in vivo with PET in comparison with other eoFAD mutations and sporadic Alzheimer disease (sAD).
Methods: We examined 2 APParc mutation carriers together with 5 noncarrier siblings cross-sectionally with 11C-labeled Pittsburgh compound B (PiB) and 18F-fluorodeoxyglucose (FDG) PET, as well as MRI, CSF biomarkers, and neuropsychological tests. Likewise, we examined 7 patients with sAD, 1 carrier of a presenilin 1 (PSEN1) mutation, 1 carrier of the Swedish APP (APPswe) mutation, and 7 healthy controls (HCs).
Results: Cortical PiB retention was very low in the APParc mutation carriers while cerebral glucose metabolism and CSF levels of Aβ1-42, total and phosphorylated tau were clearly pathologic. This was in contrast to the PSEN1 and APPswe mutation carriers revealing high PiB retention in the cortex and the striatum in combination with abnormal glucose metabolism and CSF biomarkers, and the patients with sAD who showed typically high cortical PiB retention and pathologic CSF levels as well as decreased glucose metabolism when compared with HCs.
Conclusions: The lack of fibrillar β-amyloid (Aβ) as visualized by PiB PET in APParc mutation carriers suggests, given the reduced glucose metabolism and levels of Aβ1-42 in CSF, that other forms of Aβ such as oligomers and protofibrils are important for the pathologic processes leading to clinical Alzheimer disease.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- APParc=
- Arctic APP;
- APPswe=
- Swedish APP mutation carrier;
- CAA=
- cerebral amyloid angiopathy;
- eoFAD=
- early-onset familial Alzheimer disease;
- FDG=
- 18F-fluorodeoxyglucose;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- p-tau=
- phosphorylated tau;
- PiB=
- Pittsburgh compound B;
- sAD=
- sporadic Alzheimer disease;
- t-tau=
- total tau;
- varAD=
- variant AD
Footnotes
Study funding: Supported by grants from the Knut and Alice Wallenberg Foundation, the Strategic Research Program in Neuroscience at Karolinska Institutet, the Swedish Research Council (project 05817 and 21738), the Swedish Brain Power, the Marianne and Marcus Wallenberg Foundation, the King Gustaf V and Queen Victoria's Foundation of Freemasons, the Old Servants Foundation, the Gun and Bertil Stohne's Foundation, the Brain Foundation, the Swedish Alzheimer Foundation, and the Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and the Karolinska Institutet.
Editorial, page 206
Supplemental data at www.neurology.org
- Received September 2, 2011.
- Accepted December 1, 2011.
- Copyright © 2012 by AAN Enterprises, Inc.
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
Cutaneous α-Synuclein Signatures in Patients With Multiple System Atrophy and Parkinson Disease
Dr. Rizwan S. Akhtar and Dr. Sarah Brooker
► Watch
Related Articles
Topics Discussed
Alert Me
Recommended articles
-
Articles
APOE modifies the association between Aβ load and cognition in cognitively normal older adultsK. Kantarci, V. Lowe, S.A. Przybelski et al.Neurology, December 21, 2011 -
Article
Amyloid is linked to cognitive decline in patients with Parkinson disease without dementiaStephen N. Gomperts, Joseph J. Locascio, Dorene Rentz et al.Neurology, December 12, 2012 -
Articles
Conversion of amyloid positive and negative MCI to AD over 3 yearsAn 11C-PIB PET studyA. Okello, J. Koivunen, P. Edison et al.Neurology, July 08, 2009 -
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