Neurobiology of Aging
Volume 27, Issue 10 , Pages 1416-1424, October 2006

Apolipoprotein E epsilon4 is associated with atrophy of the amygdala in Alzheimer's disease

  • Michael Basso

      Affiliations

    • Alzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, One Church Street, Suite 600, New Haven, CT 06510, USA
  • ,
  • Joel Gelernter

      Affiliations

    • Division of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
  • ,
  • John Yang

      Affiliations

    • Alzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, One Church Street, Suite 600, New Haven, CT 06510, USA
  • ,
  • Martha G. MacAvoy

      Affiliations

    • Alzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, One Church Street, Suite 600, New Haven, CT 06510, USA
  • ,
  • Pradeep Varma

      Affiliations

    • Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA
  • ,
  • Richard A. Bronen

      Affiliations

    • Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT, USA
  • ,
  • Christopher H. van Dyck

      Affiliations

    • Alzheimer's Disease Research Unit, Department of Psychiatry, Yale University School of Medicine, One Church Street, Suite 600, New Haven, CT 06510, USA
    • Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 203 764 8100; fax: +1 203 764 8111.

Received 22 April 2005; received in revised form 30 June 2005; accepted 10 August 2005. published online 23 September 2005.

Abstract 

Although the ApoE ϵ4 allele is well-established as the most important genetic risk factor for Alzheimer's disease (AD), the effects of this allele on regional brain atrophy in AD patients remain controversial. We performed MRI-based volumetric measurements of the hippocampus and amygdala (normalized to intracranial volume) in 32 ϵ4+ AD patients, 23 ϵ4− AD patients, and 42 cognitively normal elderly control subjects. Analysis of covariance revealed that amygdaloid volume was significantly smaller (19.2%) in ApoE ϵ4+ than ϵ4− AD patients, controlling for disease severity (F=10.62; d.f.=1,52; p=0.002; ANCOVA). Alternatively, when ApoE ϵ4 dose was considered, this effect appeared to accrue from a difference between the 0ϵ4 and each of the other two AD groups, with no significant difference between the 1ϵ4 and 2ϵ4 AD groups. Hippocampal volumes and asymmetry indices for hippocampus and amygdala did not differ between ϵ4 carriers and noncarriers. These results suggest accelerated atrophy of the amygdala in AD in association with ApoE ϵ4 and provide further evidence for regionally specific effects of this allele.

Keywords: Apolipoprotein E, Alzheimer's disease, Magnetic resonance imaging, Amygdala, Hippocampus

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PII: S0197-4580(05)00224-1

doi:10.1016/j.neurobiolaging.2005.08.002

Neurobiology of Aging
Volume 27, Issue 10 , Pages 1416-1424, October 2006