Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees

William E. Klunk, Julie C. Price, Chester A. Mathis, Nicholas D. Tsopelas, Brian J. Lopresti, Scott K. Ziolko, Wenzhu Bi Mowrey, Jessica A. Hoge, Ann D. Cohen, Milos D. Ikonomovic, Judith A. Saxton, Beth E. Snitz, Daniel A. Pollen, Majaz Moonis, Carol F. Lippa, Joan M. Swearer, Keith A. Johnson, Dorene M. Rentz, Alan J. Fischman, Howard J. Aizenstein & 1 others Steven T. DeKosky

Research output: Contribution to journalArticle

267 Citations (Scopus)

Abstract

The amyloid cascade hypothesis suggests that the aggregation and deposition of amyloid-βprotein 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.

Original languageEnglish (US)
Pages (from-to)6174-6184
Number of pages11
JournalJournal of Neuroscience
Volume27
Issue number23
DOIs
StatePublished - Jun 6 2007
Externally publishedYes

Fingerprint

Presenilin-1
Pedigree
Amyloid
Alzheimer Disease
Mutation
Corpus Striatum
Positron-Emission Tomography
Amyloidogenic Proteins
Natural History
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Technology
Brain

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Diagnosis
  • Pittsburgh compound-B
  • Positron emission tomography
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Klunk, W. E., Price, J. C., Mathis, C. A., Tsopelas, N. D., Lopresti, B. J., Ziolko, S. K., ... DeKosky, S. T. (2007). Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. Journal of Neuroscience, 27(23), 6174-6184. https://doi.org/10.1523/JNEUROSCI.0730-07.2007

Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. / Klunk, William E.; Price, Julie C.; Mathis, Chester A.; Tsopelas, Nicholas D.; Lopresti, Brian J.; Ziolko, Scott K.; Mowrey, Wenzhu Bi; Hoge, Jessica A.; Cohen, Ann D.; Ikonomovic, Milos D.; Saxton, Judith A.; Snitz, Beth E.; Pollen, Daniel A.; Moonis, Majaz; Lippa, Carol F.; Swearer, Joan M.; Johnson, Keith A.; Rentz, Dorene M.; Fischman, Alan J.; Aizenstein, Howard J.; DeKosky, Steven T.

In: Journal of Neuroscience, Vol. 27, No. 23, 06.06.2007, p. 6174-6184.

Research output: Contribution to journalArticle

Klunk, WE, Price, JC, Mathis, CA, Tsopelas, ND, Lopresti, BJ, Ziolko, SK, Mowrey, WB, Hoge, JA, Cohen, AD, Ikonomovic, MD, Saxton, JA, Snitz, BE, Pollen, DA, Moonis, M, Lippa, CF, Swearer, JM, Johnson, KA, Rentz, DM, Fischman, AJ, Aizenstein, HJ & DeKosky, ST 2007, 'Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees', Journal of Neuroscience, vol. 27, no. 23, pp. 6174-6184. https://doi.org/10.1523/JNEUROSCI.0730-07.2007
Klunk, William E. ; Price, Julie C. ; Mathis, Chester A. ; Tsopelas, Nicholas D. ; Lopresti, Brian J. ; Ziolko, Scott K. ; Mowrey, Wenzhu Bi ; Hoge, Jessica A. ; Cohen, Ann D. ; Ikonomovic, Milos D. ; Saxton, Judith A. ; Snitz, Beth E. ; Pollen, Daniel A. ; Moonis, Majaz ; Lippa, Carol F. ; Swearer, Joan M. ; Johnson, Keith A. ; Rentz, Dorene M. ; Fischman, Alan J. ; Aizenstein, Howard J. ; DeKosky, Steven T. / Amyloid deposition begins in the striatum of presenilin-1 mutation carriers from two unrelated pedigrees. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 23. pp. 6174-6184.
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AU - Saxton, Judith A.

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AU - Pollen, Daniel A.

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AU - Lippa, Carol F.

AU - Swearer, Joan M.

AU - Johnson, Keith A.

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AU - Aizenstein, Howard J.

AU - DeKosky, Steven T.

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