Reduced hippocampal CA2, CA3, and dentate gyrus activity in asymptomatic people at genetic risk for Alzheimer's disease

Nanthia A. Suthana; Allison Krupa; Markus Donix; Alison Burggren; Arne D. Ekstrom; Michael Jones; Linda M. Ercoli; Karen J. Miller; Prabha Siddarth; Gary W. Small; Susan Y. Bookheimer

doi:10.1016/j.neuroimage.2009.12.014

Reduced hippocampal CA2, CA3, and dentate gyrus activity in asymptomatic people at genetic risk for Alzheimer's disease

Nanthia A. Suthana, Allison Krupa, Markus Donix, Alison Burggren, Arne D. Ekstrom, Michael Jones, Linda M. Ercoli, Karen J. Miller, Prabha Siddarth, Gary W. Small, Susan Y. Bookheimer

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Previous functional magnetic resonance imaging (MRI) studies in healthy subjects with the apolipoprotein Eε4 (APOE-4) genetic risk for Alzheimer's disease have shown increased activation during memory task performance in broadly distributed cortical regions. These findings have been hypothesized to reflect compensatory recruitment of intact brain regions that presumably result from subtle neural dysfunction reflecting incipient disease. In this study, we used high-resolution functional MRI in APOE-4 carriers and non-carriers to measure activity in hippocampal subregions (CA fields 1, 2, 3; dentate gyrus [DG], and subiculum) and adjacent medial temporal lobe (parahippocampal and entorhinal) subregions. We found reduced left CA2, CA3, and dentate gyrus (CA23DG) activity in cognitively intact APOE-4 carriers. These results suggest that reduced neural activity in hippocampal subregions may underlie the compensatory increase in extrahippocampal activity in people with a genetic risk for Alzheimer's disease prior to the onset of cognitive deficits.

Original language	English (US)
Pages (from-to)	1077-1084
Number of pages	8
Journal	NeuroImage
Volume	53
Issue number	3
DOIs	https://doi.org/10.1016/j.neuroimage.2009.12.014
State	Published - Nov 2010
Externally published	Yes

Keywords

Alzheimer's disease
ApoE
FMRI
High-resolution imaging
Hippocampus
MRI

ASJC Scopus subject areas

Neurology
Cognitive Neuroscience

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10.1016/j.neuroimage.2009.12.014

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@article{bdb5f38699f447d7801f80bd47b48eb8,

title = "Reduced hippocampal CA2, CA3, and dentate gyrus activity in asymptomatic people at genetic risk for Alzheimer's disease",

abstract = "Previous functional magnetic resonance imaging (MRI) studies in healthy subjects with the apolipoprotein Eε4 (APOE-4) genetic risk for Alzheimer's disease have shown increased activation during memory task performance in broadly distributed cortical regions. These findings have been hypothesized to reflect compensatory recruitment of intact brain regions that presumably result from subtle neural dysfunction reflecting incipient disease. In this study, we used high-resolution functional MRI in APOE-4 carriers and non-carriers to measure activity in hippocampal subregions (CA fields 1, 2, 3; dentate gyrus [DG], and subiculum) and adjacent medial temporal lobe (parahippocampal and entorhinal) subregions. We found reduced left CA2, CA3, and dentate gyrus (CA23DG) activity in cognitively intact APOE-4 carriers. These results suggest that reduced neural activity in hippocampal subregions may underlie the compensatory increase in extrahippocampal activity in people with a genetic risk for Alzheimer's disease prior to the onset of cognitive deficits.",

keywords = "Alzheimer's disease, ApoE, FMRI, High-resolution imaging, Hippocampus, MRI",

author = "Suthana, {Nanthia A.} and Allison Krupa and Markus Donix and Alison Burggren and Ekstrom, {Arne D.} and Michael Jones and Ercoli, {Linda M.} and Miller, {Karen J.} and Prabha Siddarth and Small, {Gary W.} and Bookheimer, {Susan Y.}",

note = "Funding Information: We thank Michael Zeineh and Paul Thompson for assistance with group unfolding scripts and James Kyle and Brian Renner for technical assistance. The authors also thank Andrea Kaplan and Debbie Dorsey for their help in subject recruitment, data management, and study coordination. This work was supported by the NIMH T90 431587-BH-29793 , NSF GK-12 0742410 , and NIA 2R01 AG013308 , P01 AG025831 , P01-AG024831 , P50 AG 16570 , and M01-RR00865 , General Clinical Research Centers Program; the Fran and Ray Stark Foundation Fund for Alzheimer's Disease Research; and the Larry L. Hillblom Foundation. No company provided support of any kind for this study. Finally, we also wish to thank all of the subjects for their participation in this study. ",

year = "2010",

month = nov,

doi = "10.1016/j.neuroimage.2009.12.014",

language = "English (US)",

volume = "53",

pages = "1077--1084",

journal = "NeuroImage",

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T1 - Reduced hippocampal CA2, CA3, and dentate gyrus activity in asymptomatic people at genetic risk for Alzheimer's disease

AU - Suthana, Nanthia A.

AU - Krupa, Allison

AU - Donix, Markus

AU - Burggren, Alison

AU - Ekstrom, Arne D.

AU - Jones, Michael

AU - Ercoli, Linda M.

AU - Miller, Karen J.

AU - Siddarth, Prabha

AU - Small, Gary W.

AU - Bookheimer, Susan Y.

N1 - Funding Information: We thank Michael Zeineh and Paul Thompson for assistance with group unfolding scripts and James Kyle and Brian Renner for technical assistance. The authors also thank Andrea Kaplan and Debbie Dorsey for their help in subject recruitment, data management, and study coordination. This work was supported by the NIMH T90 431587-BH-29793 , NSF GK-12 0742410 , and NIA 2R01 AG013308 , P01 AG025831 , P01-AG024831 , P50 AG 16570 , and M01-RR00865 , General Clinical Research Centers Program; the Fran and Ray Stark Foundation Fund for Alzheimer's Disease Research; and the Larry L. Hillblom Foundation. No company provided support of any kind for this study. Finally, we also wish to thank all of the subjects for their participation in this study.

PY - 2010/11

Y1 - 2010/11

N2 - Previous functional magnetic resonance imaging (MRI) studies in healthy subjects with the apolipoprotein Eε4 (APOE-4) genetic risk for Alzheimer's disease have shown increased activation during memory task performance in broadly distributed cortical regions. These findings have been hypothesized to reflect compensatory recruitment of intact brain regions that presumably result from subtle neural dysfunction reflecting incipient disease. In this study, we used high-resolution functional MRI in APOE-4 carriers and non-carriers to measure activity in hippocampal subregions (CA fields 1, 2, 3; dentate gyrus [DG], and subiculum) and adjacent medial temporal lobe (parahippocampal and entorhinal) subregions. We found reduced left CA2, CA3, and dentate gyrus (CA23DG) activity in cognitively intact APOE-4 carriers. These results suggest that reduced neural activity in hippocampal subregions may underlie the compensatory increase in extrahippocampal activity in people with a genetic risk for Alzheimer's disease prior to the onset of cognitive deficits.

AB - Previous functional magnetic resonance imaging (MRI) studies in healthy subjects with the apolipoprotein Eε4 (APOE-4) genetic risk for Alzheimer's disease have shown increased activation during memory task performance in broadly distributed cortical regions. These findings have been hypothesized to reflect compensatory recruitment of intact brain regions that presumably result from subtle neural dysfunction reflecting incipient disease. In this study, we used high-resolution functional MRI in APOE-4 carriers and non-carriers to measure activity in hippocampal subregions (CA fields 1, 2, 3; dentate gyrus [DG], and subiculum) and adjacent medial temporal lobe (parahippocampal and entorhinal) subregions. We found reduced left CA2, CA3, and dentate gyrus (CA23DG) activity in cognitively intact APOE-4 carriers. These results suggest that reduced neural activity in hippocampal subregions may underlie the compensatory increase in extrahippocampal activity in people with a genetic risk for Alzheimer's disease prior to the onset of cognitive deficits.

KW - Alzheimer's disease

KW - ApoE

KW - FMRI

KW - High-resolution imaging

KW - Hippocampus

KW - MRI

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JO - NeuroImage

JF - NeuroImage

IS - 3

ER -

Reduced hippocampal CA2, CA3, and dentate gyrus activity in asymptomatic people at genetic risk for Alzheimer's disease

Abstract

Keywords

ASJC Scopus subject areas

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