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Journal article
Amyloid Deposition Begins in the Striatum of Presenilin-1 Mutation Carriers from Two Unrelated Pedigrees
The Journal of neuroscience, v 27(23), pp 6174-6184
06 Jun 2007
PMCID: PMC3265970
PMID: 17553989
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The amyloid cascade hypothesis suggests that the aggregation and deposition of amyloid-β protein is an initiating event in Alzheimer's disease (AD). Using amyloid imaging technology, such as the positron emission tomography (PET) agent Pittsburgh compound-B (PiB), it is possible to explore the natural history of preclinical amyloid deposition in people at high risk for AD. With this goal in mind, asymptomatic (
n
= 5) and symptomatic (
n
= 5) carriers of presenilin-1 (PS1) mutations (C410Y or A426P) that lead to early-onset AD and noncarrier controls from both kindreds (
n
= 2) were studied with PiB–PET imaging and compared with sporadic AD subjects (
n
= 12) and controls from the general population (
n
= 18). We found intense and focal PiB retention in the striatum of all 10 PS1 mutation carriers studied (ages 35–49 years). In most PS1 mutation carriers, there also were increases in PiB retention compared with controls in cortical brain areas, but these increases were not as great as those observed in sporadic AD subjects. The two PS1 mutation carriers with a clinical diagnosis of early-onset AD did not show the typical regional pattern of PiB retention observed in sporadic AD. Postmortem evaluation of tissue from two parents of PS1C410Y subjects in this study confirmed extensive striatal amyloid deposition, along with typical cortical deposition. The early, focal striatal amyloid deposition observed in these PS1 mutation carriers is often is not associated with clinical symptoms.
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Details
- Title
- Amyloid Deposition Begins in the Striatum of Presenilin-1 Mutation Carriers from Two Unrelated Pedigrees
- Creators
- William E. Klunk - University of PittsburghJulie C. Price - University of PittsburghChester A. Mathis - University of PittsburghNicholas D. Tsopelas - University of PittsburghBrian J. Lopresti - University of PittsburghScott K. Ziolko - University of PittsburghWenzhu Bi - University of PittsburghJessica A. Hoge - University of PittsburghAnn D. Cohen - University of PittsburghMilos D. Ikonomovic - University of PittsburghJudith A. Saxton - University of PittsburghBeth E. Snitz - University of PittsburghDaniel A. Pollen - University of Massachusetts Medical SchoolMajaz Moonis - University of Massachusetts Medical SchoolCarol F. Lippa - Drexel UniversityJoan M. Swearer - University of Massachusetts Medical SchoolKeith A. Johnson - Harvard University ,Dorene M. Rentz - Harvard University ,Alan J. Fischman - Harvard University ,Howard J. Aizenstein - University of PittsburghSteven T. DeKosky - University of Pittsburgh
- Publication Details
- The Journal of neuroscience, v 27(23), pp 6174-6184
- Publisher
- Society for Neuroscience
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000247049300011
- Scopus ID
- 2-s2.0-34249984684
- Other Identifier
- 991019312466604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences