The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume

Michelle K. Lupton; Lachlan Strike; Narelle K. Hansell; Wei Wen; Karen A. Mather; Nicola J. Armstrong; Anbupalam Thalamuthu; Katie L. McMahon; Greig I. de Zubicaray; Amelia A. Assareh; Andrew Simmons; Petroula Proitsi; John F. Powell; Grant W. Montgomery; Derrek P. Hibar; Eric Westman; Magda Tsolaki; Iwona Kloszewska; Hilkka Soininen; Patrizia Mecocci; Bruno Velas; Simon Lovestone; Henry Brodaty; David Ames; Julian N. Trollor; Nicholas G. Martin; Paul M. Thompson; Perminder S. Sachdev; Margaret J. Wright

doi:10.1016/j.neurobiolaging.2015.12.023

The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume

Michelle K. Lupton^*, Lachlan Strike, Narelle K. Hansell, Wei Wen, Karen A. Mather, Nicola J. Armstrong, Anbupalam Thalamuthu, Katie L. McMahon, Greig I. de Zubicaray, Amelia A. Assareh, Andrew Simmons, Petroula Proitsi, John F. Powell, Grant W. Montgomery, Derrek P. Hibar, Eric Westman, Magda Tsolaki, Iwona Kloszewska, Hilkka Soininen, Patrizia MecocciBruno Velas, Simon Lovestone, Henry Brodaty, David Ames, Julian N. Trollor, Nicholas G. Martin, Paul M. Thompson, Perminder S. Sachdev, Margaret J. Wright

^*Corresponding author for this work

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Abstract

Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer's disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16-30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ε4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults.

Original language	English
Pages (from-to)	68-77
Number of pages	10
Journal	Neurobiology of Aging
Volume	40
Early online date	11 Jan 2016
DOIs	https://doi.org/10.1016/j.neurobiolaging.2015.12.023
Publication status	Published - 1 Apr 2016

Keywords

Alzheimer's disease
Amygdala
APOE
Hippocampus
Polygenic risk score
TREM2

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10.1016/j.neurobiolaging.2015.12.023

The effect of increased_LUPTON_Publishedonline11January2016_GREEN AAMAccepted author manuscript, 940 KBLicence: CC BY-NC-ND

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Lupton, M. K., Strike, L., Hansell, N. K., Wen, W., Mather, K. A., Armstrong, N. J., Thalamuthu, A., McMahon, K. L., de Zubicaray, G. I., Assareh, A. A., Simmons, A., Proitsi, P., Powell, J. F., Montgomery, G. W., Hibar, D. P., Westman, E., Tsolaki, M., Kloszewska, I., Soininen, H., ... Wright, M. J. (2016). The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume. Neurobiology of Aging, 40, 68-77. https://doi.org/10.1016/j.neurobiolaging.2015.12.023

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abstract = "Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer's disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16-30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ε4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults.",

keywords = "Alzheimer's disease, Amygdala, APOE, Hippocampus, Polygenic risk score, TREM2",

author = "Lupton, {Michelle K.} and Lachlan Strike and Hansell, {Narelle K.} and Wei Wen and Mather, {Karen A.} and Armstrong, {Nicola J.} and Anbupalam Thalamuthu and McMahon, {Katie L.} and {de Zubicaray}, {Greig I.} and Assareh, {Amelia A.} and Andrew Simmons and Petroula Proitsi and Powell, {John F.} and Montgomery, {Grant W.} and Hibar, {Derrek P.} and Eric Westman and Magda Tsolaki and Iwona Kloszewska and Hilkka Soininen and Patrizia Mecocci and Bruno Velas and Simon Lovestone and Henry Brodaty and David Ames and Trollor, {Julian N.} and Martin, {Nicholas G.} and Thompson, {Paul M.} and Sachdev, {Perminder S.} and Wright, {Margaret J.}",

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Lupton, MK, Strike, L, Hansell, NK, Wen, W, Mather, KA, Armstrong, NJ, Thalamuthu, A, McMahon, KL, de Zubicaray, GI, Assareh, AA, Simmons, A , Proitsi, P , Powell, JF, Montgomery, GW, Hibar, DP, Westman, E, Tsolaki, M, Kloszewska, I, Soininen, H, Mecocci, P, Velas, B, Lovestone, S, Brodaty, H, Ames, D, Trollor, JN, Martin, NG, Thompson, PM, Sachdev, PS & Wright, MJ 2016, 'The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume', Neurobiology of Aging, vol. 40, pp. 68-77. https://doi.org/10.1016/j.neurobiolaging.2015.12.023

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AU - Lupton, Michelle K.

AU - Strike, Lachlan

AU - Hansell, Narelle K.

AU - Wen, Wei

AU - Mather, Karen A.

AU - Armstrong, Nicola J.

AU - Thalamuthu, Anbupalam

AU - McMahon, Katie L.

AU - de Zubicaray, Greig I.

AU - Assareh, Amelia A.

AU - Simmons, Andrew

AU - Proitsi, Petroula

AU - Powell, John F.

AU - Montgomery, Grant W.

AU - Hibar, Derrek P.

AU - Westman, Eric

AU - Tsolaki, Magda

AU - Kloszewska, Iwona

AU - Soininen, Hilkka

AU - Mecocci, Patrizia

AU - Velas, Bruno

AU - Lovestone, Simon

AU - Brodaty, Henry

AU - Ames, David

AU - Trollor, Julian N.

AU - Martin, Nicholas G.

AU - Thompson, Paul M.

AU - Sachdev, Perminder S.

AU - Wright, Margaret J.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer's disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16-30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ε4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults.

AB - Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer's disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16-30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ε4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults.

KW - Alzheimer's disease

KW - Amygdala

KW - APOE

KW - Hippocampus

KW - Polygenic risk score

KW - TREM2

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DO - 10.1016/j.neurobiolaging.2015.12.023

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SN - 0197-4580

VL - 40

SP - 68

EP - 77

JO - Neurobiology of Aging

JF - Neurobiology of Aging

ER -

The effect of increased genetic risk for Alzheimer's disease on hippocampal and amygdala volume

Abstract

Keywords

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