title: Impact of apolipoprotein E4-cerebrospinal fluid β-amyloid interaction on hippocampal volume loss over 1 year in mild cognitive impairment.
abstract: BACKGROUND
  The majority of studies relating amyloid pathology with brain volumes have been cross-sectional. Apolipoprotein ɛ4 (APOE ɛ4), 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 ɛ4 together on longitudinal volume loss.
  
  
  METHODS
  We evaluated whether an abnormal level of cerebrospinal fluid beta-amyloid (CSF Aβ) and APOE ɛ4 carrier status were independently associated with greater hippocampal volume loss over 1 year. We then assessed whether APOE ɛ4 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 ɛ4 was associated with hippocampal volume loss only in the cognitively normal and MCI groups. APOE ɛ4 carriers with abnormal CSF Aβ in the MCI group acted synergistically to produce disproportionately greater volume loss than noncarriers.
  
  
  CONCLUSIONS
  Baseline CSF Aβ predicts progression of hippocampal volume loss. APOE ɛ4 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.
authors: Department of Radiology, University of California, San Francisco, USA. gloria.chiang@radiology.ucsf.edu
authors: Gloria C
authors: GC
authors: Chiang
authors: Philip S
authors: PS
authors: Insel
authors: Duygu
authors: D
authors: Tosun
authors: Norbert
authors: N
authors: Schuff
authors: Diana
authors: D
authors: Truran-Sacrey
authors: Sky T
authors: ST
authors: Raptentsetsang
authors: Paul M
authors: PM
authors: Thompson
authors: Eric M
authors: EM
authors: Reiman
authors: Clifford R
authors: CR
authors: Jack
authors: Nick C
authors: NC
authors: Fox
authors: William J
authors: WJ
authors: Jagust
authors: Danielle J
authors: DJ
authors: Harvey
authors: Laurel A
authors: LA
authors: Beckett
authors: Anthony
authors: A
authors: Gamst
authors: Paul S
authors: PS
authors: Aisen
authors: Ron C
authors: RC
authors: Petersen
authors: Michael W
authors: MW
authors: Weiner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4