Impact of apolipoprotein varepsilon4-cerebrospinal fluid beta-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment

Background: The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein 3 4( APOE 34), 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 34 together on longitudinal volume loss. Methods: We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Ab) and APOE 34 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE 34 status and CSF Ab 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 Ab level was found to be associated with greater hippocampal volume loss over 1 year in each group. APOE 34 was associated with hippocampal volume loss only in the cognitivelynormal andMCIgroups.APOE34carrierswith abnormalCSFAbintheMCIgroupacted synergistically to produce disproportionately greater volume loss than noncarriers. Conclusion: Baseline CSF Ab predicts progression of hippocampal volume loss. APOE 34 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. 2011 The Alzheimer’s Association. All rights reserved.