Memory performance is related to amyloid and tau pathology in the hippocampus
- 1Gertrude H Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, New York, USA
- 2The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University College of Physicians and Surgeons, New York, New York, USA
- 3The Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York, USA
- 4The Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA
- 5The Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York, USA
- 6The Department of Biostatistics in the Mailman School of Public Health, Columbia University College of Physicians and Surgeons, New York, New York, USA
- 7The Department of Epidemiology in the Mailman School of Public Health, Columbia University College of Physicians and Surgeons, New York, New York, USA
- Dr C Reitz, Gertrude H Sergievsky Center/Taub Institute for Research on the Aging Brain, 630 West 168th Street, Columbia University, New York, NY 10032, USA; cr2101{at}columbia.edu
- Received 17 May 2008
- Revised 10 December 2008
- Accepted 8 January 2009
- Published Online First 3 March 2009
Abstract
Objective: To determine the relation of amyloid and tau pathology in the hippocampal formation to decline in memory and other cognitive functions in Alzheimer’s disease (AD).
Methods: Regression models were used to relate semiquantitative measurements of amyloid plaques, neurofibrillary tangles (NFTs) and neuropil threads (NTs) at autopsy with antemortem performance in memory, abstract/visuospatial and language domains in two independent samples (n = 41, n = 66) that had repeated neuropsychological measurements before death.
Results: In both groups, the number of NFTs in the entorhinal cortex, subiculum and CA1 region was inversely associated with memory performance at the last visit before death. However, the number of amyloid plaques and NTs in the entorhinal cortex was also inversely related to poor memory function. Moreover, as the number of plaques or NTs increased in any region of the hippocampal formation, there was a more rapid decline in memory performance over time; a similar decline was associated with increasing numbers of NFTs in the CA1 or subiculum. In contrast, there was no association between amyloid plaques, NFTs or NTs in the frontal or parietal lobe and performance in memory, nor was there an association between plaques, NFTs or NTs in the hippocampal formation and cognitive functions unrelated to memory.
Discussion: This study implicates both amyloid deposition and tau pathology in the hippocampus as an early and late cause of decline in memory function over time in AD. Memory performance appears to be specifically related to the amount of amyloid plaques, NFTs and NTs in the entorhinal cortex and hippocampus.
Footnotes
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Competing interests: None.
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Funding: This study was supported by grants PO1 AG07232, P50 AG08702 and RR00645 from the National Institute on Aging (Bethesda, Maryland), the Charles S Robertson Memorial Gift for Research in Alzheimer’s disease and the Blanchette Hooker Rockefeller Foundation (New York, New York).
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Ethics approval: The study was approved by Columbia University Institutional Review Board.
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See Editorial Commentary, p 703
