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

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

doi:10.1016/j.neurobiolaging.2008.09.012

« Previous Next »Neurobiology of Aging
Volume 31, Issue 10 , Pages 1669-1678, October 2010

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

Meredith N. Braskie
- Helen Wills Neuroscience Institute, University of California Berkeley, CA 94720, USA
- Ahmanson-Lovelace Brain Mapping Center, David Geffen School of Medicine at UCLA, CA 90095, USA
Andrea D. Klunder
- Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine at UCLA, CA 90095, USA
Kiralee M. Hayashi
- Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine at UCLA, CA 90095, USA
Hillary Protas
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, CA 90095, USA
- Department of Biomathematics, David Geffen School of Medicine at UCLA, CA 90095, USA
Vladimir Kepe
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, CA 90095, USA
Karen J. Miller
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, CA 90095, USA
S.-C. Huang
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, CA 90095, USA
Jorge R. Barrio
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, CA 90095, USA
Linda M. Ercoli
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, CA 90095, USA
Prabha Siddarth
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, CA 90095, USA
Nagichettiar Satyamurthy
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, CA 90095, USA
Jie Liu
- Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, CA 90095, USA
Arthur W. Toga
- Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine at UCLA, CA 90095, USA
Susan Y. Bookheimer
- Ahmanson-Lovelace Brain Mapping Center, David Geffen School of Medicine at UCLA, CA 90095, USA
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, CA 90095, USA
- Department of Psychology, David Geffen School of Medicine at UCLA, CA 90095, USA
Gary W. Small
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, CA 90095, USA
- UCLA Center on Aging, CA 90095, USA
Paul M. Thompson
- Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine at UCLA, CA 90095, USA
- Corresponding author at: Laboratory of Neuro Imaging, Department of Neurology, David Geffen School of Medicine at UCLA, 635 Charles E. Young Drive South, Suite 225E, Los Angeles, CA 90095-7332, USA. Tel.: +1 310 206 2101; fax: +1 310 206 5518.

Received 26 March 2008; received in revised form 9 July 2008; accepted 22 September 2008. published online 12 November 2008.

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.

Keywords: Amyloid, Cerebral cortex, Cognitive aging, Memory, PET