Plaque and tangle imaging and cognition in normal aging and Alzheimer's disease

Meredith N. Braskie, Andrea D. Klunder, Kiralee M. Hayashi, Hillary Protas, Vladimir Kepe, Karen J. Miller, S. C. Huang, Jorge R. Barrio, Linda M. Ercoli, Prabha Siddarth, Nagichettiar Satyamurthy, Jie Liu, Arthur W. Toga, Susan Y. Bookheimer, Gary W. Small, Paul M. Thompson

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

Amyloid plaques and tau neurofibrillary tangles, the pathological hallmarks of Alzheimer's disease (AD), begin accumulating in the healthy human brain decades before clinical dementia symptoms can be detected. There is great interest in how this pathology spreads in the living brain and its association with cognitive deterioration. Using MRI-derived cortical surface models and four-dimensional animation techniques, we related cognitive ability to positron emission tomography (PET) signal from 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP), a molecular imaging probe for plaques and tangles. We examined this relationship at each cortical surface point in 23 older adults (10 cognitively intact, 6 with amnestic mild cognitive impairment, 7 with AD). [18F]FDDNP-PET signal was highly correlated with cognitive performance, even in cognitively intact subjects. Animations of [18F]FDDNP signal growth with decreased cognition across all subjects (http://www.loni.ucla.edu/∼thompson/FDDNP/video.html) mirrored the classic Braak and Braak trajectory in lateral temporal, parietal, and frontal cortices. Regions in which cognitive performance was significantly correlated with [18F]FDDNP signal include those that deteriorate earliest in AD, suggesting the potential utility of [18F]FDDNP for early diagnosis.

Original languageEnglish
Pages (from-to)1669-1678
Number of pages10
JournalNeurobiology of Aging
Volume31
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Keywords

  • Amyloid
  • Cerebral cortex
  • Cognitive aging
  • Memory
  • PET

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