Impact of apolipoprotein ε4-cerebrospinal fluid beta-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment

Gloria C. Chiang, Philip S. Insel, Duygu Tosun, Norbert Schuff, Diana Truran-Sacrey, Sky T. Raptentsetsang, Paul M. Thompson, Eric M. Reiman, Clifford R Jr. Jack, Nick C. Fox, William J. Jagust, Danielle J. Harvey, Laurel A. Beckett, Anthony Gamst, Paul S. Aisen, Ronald Carl Petersen, Michael W. Weiner

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein ε4 (APOE ε4), a genetic risk factor for Alzheimer's disease, is also known to be associated with hippocampal volume loss. No studies have considered the effects of amyloid pathology and APOE ε4 together on longitudinal volume loss. Methods: We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Aβ) and APOE ε4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE ε4 status and CSF Aβ acted synergistically, testing the significance of an interaction term in the regression analysis. We included 297 participants: 77 cognitively normal, 144 with mild cognitive impairment (MCI), and 76 with Alzheimer's disease. Results: An abnormal CSF Aβ level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE ε4 was associated with hippocampal volume loss only in the cognitively normal and MCI groups. APOE ε4 carriers with abnormal CSF Aβ in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers. Conclusion: Baseline CSF Aβ predicts progression of hippocampal volume loss. APOE ε4 carrier status amplifies the degree of neurodegeneration in MCI. Understanding the effect of interactions between genetic risk and amyloid pathology will be important in clinical trials and our understanding of the disease process.

Original languageEnglish (US)
Pages (from-to)514-520
Number of pages7
JournalAlzheimer's and Dementia
Volume7
Issue number5
DOIs
StatePublished - Sep 2011

Fingerprint

Apolipoproteins
Amyloid
Cerebrospinal Fluid
Pathology
Alzheimer Disease
Cognitive Dysfunction
Regression Analysis
Clinical Trials
Brain

Keywords

  • Apolipoprotein E4
  • Beta-amyloid
  • Biomarker
  • Hippocampal atrophy
  • MRI

ASJC Scopus subject areas

  • Health Policy
  • Epidemiology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Clinical Neurology
  • Medicine(all)

Cite this

Chiang, G. C., Insel, P. S., Tosun, D., Schuff, N., Truran-Sacrey, D., Raptentsetsang, S. T., ... Weiner, M. W. (2011). Impact of apolipoprotein ε4-cerebrospinal fluid beta-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment. Alzheimer's and Dementia, 7(5), 514-520. https://doi.org/10.1016/j.jalz.2010.12.010

Impact of apolipoprotein ε4-cerebrospinal fluid beta-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment. / Chiang, Gloria C.; Insel, Philip S.; Tosun, Duygu; Schuff, Norbert; Truran-Sacrey, Diana; Raptentsetsang, Sky T.; Thompson, Paul M.; Reiman, Eric M.; Jack, Clifford R Jr.; Fox, Nick C.; Jagust, William J.; Harvey, Danielle J.; Beckett, Laurel A.; Gamst, Anthony; Aisen, Paul S.; Petersen, Ronald Carl; Weiner, Michael W.

In: Alzheimer's and Dementia, Vol. 7, No. 5, 09.2011, p. 514-520.

Research output: Contribution to journalArticle

Chiang, GC, Insel, PS, Tosun, D, Schuff, N, Truran-Sacrey, D, Raptentsetsang, ST, Thompson, PM, Reiman, EM, Jack, CRJ, Fox, NC, Jagust, WJ, Harvey, DJ, Beckett, LA, Gamst, A, Aisen, PS, Petersen, RC & Weiner, MW 2011, 'Impact of apolipoprotein ε4-cerebrospinal fluid beta-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment', Alzheimer's and Dementia, vol. 7, no. 5, pp. 514-520. https://doi.org/10.1016/j.jalz.2010.12.010
Chiang, Gloria C. ; Insel, Philip S. ; Tosun, Duygu ; Schuff, Norbert ; Truran-Sacrey, Diana ; Raptentsetsang, Sky T. ; Thompson, Paul M. ; Reiman, Eric M. ; Jack, Clifford R Jr. ; Fox, Nick C. ; Jagust, William J. ; Harvey, Danielle J. ; Beckett, Laurel A. ; Gamst, Anthony ; Aisen, Paul S. ; Petersen, Ronald Carl ; Weiner, Michael W. / Impact of apolipoprotein ε4-cerebrospinal fluid beta-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment. In: Alzheimer's and Dementia. 2011 ; Vol. 7, No. 5. pp. 514-520.
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AU - Chiang, Gloria C.

AU - Insel, Philip S.

AU - Tosun, Duygu

AU - Schuff, Norbert

AU - Truran-Sacrey, Diana

AU - Raptentsetsang, Sky T.

AU - Thompson, Paul M.

AU - Reiman, Eric M.

AU - Jack, Clifford R Jr.

AU - Fox, Nick C.

AU - Jagust, William J.

AU - Harvey, Danielle J.

AU - Beckett, Laurel A.

AU - Gamst, Anthony

AU - Aisen, Paul S.

AU - Petersen, Ronald Carl

AU - Weiner, Michael W.

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N2 - Background: The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein ε4 (APOE ε4), a genetic risk factor for Alzheimer's disease, is also known to be associated with hippocampal volume loss. No studies have considered the effects of amyloid pathology and APOE ε4 together on longitudinal volume loss. Methods: We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Aβ) and APOE ε4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE ε4 status and CSF Aβ acted synergistically, testing the significance of an interaction term in the regression analysis. We included 297 participants: 77 cognitively normal, 144 with mild cognitive impairment (MCI), and 76 with Alzheimer's disease. Results: An abnormal CSF Aβ level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE ε4 was associated with hippocampal volume loss only in the cognitively normal and MCI groups. APOE ε4 carriers with abnormal CSF Aβ in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers. Conclusion: Baseline CSF Aβ predicts progression of hippocampal volume loss. APOE ε4 carrier status amplifies the degree of neurodegeneration in MCI. Understanding the effect of interactions between genetic risk and amyloid pathology will be important in clinical trials and our understanding of the disease process.

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