Multimodal hippocampal and amygdala subfield volumetry in polygenic risk for Alzheimer's disease

Amy N. Murray; Hannah L. Chandler; Thomas M. Lancaster

doi:10.1016/j.neurobiolaging.2020.08.022

Multimodal hippocampal and amygdala subfield volumetry in polygenic risk for Alzheimer's disease

Amy N. Murray, Hannah L. Chandler, Thomas M. Lancaster

Department of Psychology

Cardiff University

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

12 Citations (SciVal)

Abstract

Preclinical models of Alzheimer's disease (AD) suggest that volumetric reductions in medial temporal lobe (MTL) structures manifest before clinical onset. AD polygenic risk scores (PRSs) are further linked to reduced MTL volumes (the hippocampus/amygdala); however, the relationship between the PRS and specific subregions remains unclear. We determine the relationship between the AD-PRSs and MTL subregions in a large sample of young participants (N = 730, aged 22–35 years) using a multimodal (T1w/T2w) approach. We first demonstrate that the PRSs for the hippocampus/amygdala predict their respective volumes and specific hippocampal subregions (pFDR < 0.05). We further observe negative relationships between the AD-PRSs and whole hippocampal/amygdala volumes. Critically, we demonstrate novel associations between the AD-PRSs and specific hippocampal subfields such as CA1 (β = −0.096, pFDR = 0.045) and the fissure (β = −0.101, pFDR = 0.041). We provide evidence that the AD-PRS is linked to specific MTL subfields decades before AD onset. This may help inform preclinical models of AD risk, providing additional specificity for intervention and further insight into mechanisms by which common AD variants confer susceptibility.

Original language	English
Pages (from-to)	33-41
Number of pages	9
Journal	Neurobiology of Aging
Volume	98
Early online date	2 Nov 2020
DOIs	https://doi.org/10.1016/j.neurobiolaging.2020.08.022
Publication status	Published - 28 Feb 2021

Bibliographical note

Funding Information:
Data were provided by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and centers that support the NIH Blueprint for Neuroscience Research and by the McDonnell Center for Systems Neuroscience at Washington University.

Funding Information:
This project was supported by Dementia Project UK (DPUK) and the Dementia Research Institute (DRI). The authors thank the MRC Centre for Neuropsychiatric Genetics and Genomics for supporting this project. H.L.C. was funded by a Wellcome Strategic Award ( 104943/Z/14/Z ). T.M.L. acknowledges funding via a Wellcome Trust ISSF Fellowship ( 513688 ) and a Sêr Cymru II Fellowship ( East Wales European Regional Development Funds [ PNU-80762-CU-14 ]).

Publisher Copyright:
© 2020 The Authors

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

Alzheimer's disease
Amygdala
Hippocampus
Multimodal MRI
Polygenic

ASJC Scopus subject areas

General Neuroscience
Ageing
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2020.08.022

Cite this

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title = "Multimodal hippocampal and amygdala subfield volumetry in polygenic risk for Alzheimer's disease",

abstract = "Preclinical models of Alzheimer's disease (AD) suggest that volumetric reductions in medial temporal lobe (MTL) structures manifest before clinical onset. AD polygenic risk scores (PRSs) are further linked to reduced MTL volumes (the hippocampus/amygdala); however, the relationship between the PRS and specific subregions remains unclear. We determine the relationship between the AD-PRSs and MTL subregions in a large sample of young participants (N = 730, aged 22–35 years) using a multimodal (T1w/T2w) approach. We first demonstrate that the PRSs for the hippocampus/amygdala predict their respective volumes and specific hippocampal subregions (pFDR < 0.05). We further observe negative relationships between the AD-PRSs and whole hippocampal/amygdala volumes. Critically, we demonstrate novel associations between the AD-PRSs and specific hippocampal subfields such as CA1 (β = −0.096, pFDR = 0.045) and the fissure (β = −0.101, pFDR = 0.041). We provide evidence that the AD-PRS is linked to specific MTL subfields decades before AD onset. This may help inform preclinical models of AD risk, providing additional specificity for intervention and further insight into mechanisms by which common AD variants confer susceptibility.",

keywords = "Alzheimer's disease, Amygdala, Hippocampus, Multimodal MRI, Polygenic",

author = "Murray, {Amy N.} and Chandler, {Hannah L.} and Lancaster, {Thomas M.}",

note = "Funding Information: Data were provided by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and centers that support the NIH Blueprint for Neuroscience Research and by the McDonnell Center for Systems Neuroscience at Washington University. Funding Information: This project was supported by Dementia Project UK (DPUK) and the Dementia Research Institute (DRI). The authors thank the MRC Centre for Neuropsychiatric Genetics and Genomics for supporting this project. H.L.C. was funded by a Wellcome Strategic Award ( 104943/Z/14/Z ). T.M.L. acknowledges funding via a Wellcome Trust ISSF Fellowship ( 513688 ) and a S{\^e}r Cymru II Fellowship ( East Wales European Regional Development Funds [ PNU-80762-CU-14 ]). Publisher Copyright: {\textcopyright} 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

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doi = "10.1016/j.neurobiolaging.2020.08.022",

language = "English",

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AU - Murray, Amy N.

AU - Chandler, Hannah L.

AU - Lancaster, Thomas M.

N1 - Funding Information: Data were provided by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and centers that support the NIH Blueprint for Neuroscience Research and by the McDonnell Center for Systems Neuroscience at Washington University. Funding Information: This project was supported by Dementia Project UK (DPUK) and the Dementia Research Institute (DRI). The authors thank the MRC Centre for Neuropsychiatric Genetics and Genomics for supporting this project. H.L.C. was funded by a Wellcome Strategic Award ( 104943/Z/14/Z ). T.M.L. acknowledges funding via a Wellcome Trust ISSF Fellowship ( 513688 ) and a Sêr Cymru II Fellowship ( East Wales European Regional Development Funds [ PNU-80762-CU-14 ]). Publisher Copyright: © 2020 The Authors Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2021/2/28

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N2 - Preclinical models of Alzheimer's disease (AD) suggest that volumetric reductions in medial temporal lobe (MTL) structures manifest before clinical onset. AD polygenic risk scores (PRSs) are further linked to reduced MTL volumes (the hippocampus/amygdala); however, the relationship between the PRS and specific subregions remains unclear. We determine the relationship between the AD-PRSs and MTL subregions in a large sample of young participants (N = 730, aged 22–35 years) using a multimodal (T1w/T2w) approach. We first demonstrate that the PRSs for the hippocampus/amygdala predict their respective volumes and specific hippocampal subregions (pFDR < 0.05). We further observe negative relationships between the AD-PRSs and whole hippocampal/amygdala volumes. Critically, we demonstrate novel associations between the AD-PRSs and specific hippocampal subfields such as CA1 (β = −0.096, pFDR = 0.045) and the fissure (β = −0.101, pFDR = 0.041). We provide evidence that the AD-PRS is linked to specific MTL subfields decades before AD onset. This may help inform preclinical models of AD risk, providing additional specificity for intervention and further insight into mechanisms by which common AD variants confer susceptibility.

AB - Preclinical models of Alzheimer's disease (AD) suggest that volumetric reductions in medial temporal lobe (MTL) structures manifest before clinical onset. AD polygenic risk scores (PRSs) are further linked to reduced MTL volumes (the hippocampus/amygdala); however, the relationship between the PRS and specific subregions remains unclear. We determine the relationship between the AD-PRSs and MTL subregions in a large sample of young participants (N = 730, aged 22–35 years) using a multimodal (T1w/T2w) approach. We first demonstrate that the PRSs for the hippocampus/amygdala predict their respective volumes and specific hippocampal subregions (pFDR < 0.05). We further observe negative relationships between the AD-PRSs and whole hippocampal/amygdala volumes. Critically, we demonstrate novel associations between the AD-PRSs and specific hippocampal subfields such as CA1 (β = −0.096, pFDR = 0.045) and the fissure (β = −0.101, pFDR = 0.041). We provide evidence that the AD-PRS is linked to specific MTL subfields decades before AD onset. This may help inform preclinical models of AD risk, providing additional specificity for intervention and further insight into mechanisms by which common AD variants confer susceptibility.

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KW - Amygdala

KW - Hippocampus

KW - Multimodal MRI

KW - Polygenic

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M3 - Article

AN - SCOPUS:85096403422

SN - 0197-4580

VL - 98

SP - 33

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JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

Multimodal hippocampal and amygdala subfield volumetry in polygenic risk for Alzheimer's disease

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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