title: Absence of an apolipoprotein E epsilon4 allele is associated with increased parietal regional cerebral blood flow asymmetry in Alzheimer disease.
abstract: BACKGROUND
  The apolipoprotein E (Apo E) epsilon4 allele has been associated with parietal metabolic abnormalities and asymmetries in asymptomatic subjects at risk for Alzheimer disease (AD). However, previous research has shown minimal effect of the epsilon4 allele on regional cerebral blood flow (rCBF) and metabolism in patients with probable AD.
  
  
  OBJECTIVE
  To determine whether the Apo E epsilon4 allele is associated with parietal rCBF abnormalities and asymmetries in patients with probable AD.
  
  
  METHODS
  Thirty patients with AD with the epsilon4 allele (epsilon4+ AD), 22 patients with AD without the epsilon4 allele (epsilon4- AD), and 14 healthy control subjects underwent single-photon emission computed tomography (SPECT) scanning with 740 MBq technetium Tc 99m hexamethylpropyleneamine oxime. Ratios of parietal-unaffected regions and a left-right parietal asymmetry index were compared between both patient groups.
  
  
  RESULTS
  The group with epsilon4- AD was younger (P = .005, Student t test) and had an earlier age of onset (P = .005) than the group with epsilon4+ AD. Analysis of covariance revealed no significant difference in the parietal rCBF ratio, controlling for age of onset and Mini-Mental State Examination score (F(1,48) = 0.06; P = .81). However, contrary to hypothesis, significantly greater parietal rCBF asymmetry was seen in patients with epsilon4- AD (mean +/- SD, 9.7% +/- 5.5%) than those with epsilon4+ AD (6.3% +/- 4.7%; F(1,50) = 5.89; P = .02; analysis of variance). When number of epsilon4 allele copies was considered, this effect appeared to accrue primarily from a difference between patients with 0 and with 2 epsilon4 allele copies. An exploratory analysis of multiple cortical structures suggested that this asymmetry extended to additional regions (superior temporal) and to combined association cortex.
  
  
  CONCLUSIONS
  Greater parietal rCBF asymmetry is involved in epsilon4- AD than in epsilon4+ AD. Lack of the epsilon4 allele may be associated with other (as yet undiscovered) genetic or environmental risk factors, which confer greater neuropathological asymmetry.
authors.affiliation: Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, Conn 06520, USA. christopher.vandyck@yale.edu
authors.forename: C H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: J
authors.initials: J
authors.lastname: Gelernter
authors.forename: M G
authors.initials: MG
authors.lastname: MacAvoy
authors.forename: R A
authors.initials: RA
authors.lastname: Avery
authors.forename: M
authors.initials: M
authors.lastname: Criden
authors.forename: O
authors.initials: O
authors.lastname: Okereke
authors.forename: P
authors.initials: P
authors.lastname: Varma
authors.forename: J P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: P B
authors.initials: PB
authors.lastname: Hoffer
mesh_terms: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics / Q000503:physiopathology*; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics*; D001931:Brain Mapping; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010296:Parietal Lobe / Q000098:blood supply*; D012307:Risk Factors; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001057:Apolipoproteins E