Absence of an apolipoprotein E ε4 allele is associated with increased parietal regional cerebral blood flow asymmetry in Alzheimer disease

Background: The apolipoprotein E (Apo E) epsilon 4 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 epsilon 4 allele on regional cerebral blood flow (rCBF) and metabolism in patients with probable AD. Objective: To determine whether the Apo E epsilon 4 allele is associated with parietal rCBF abnormalities and asymmetries in patients with probable AD. Patients and Methods: Thirty patients with AD with the epsilon 4 allele (epsilon 4+ AD), 22 patients with AD without the epsilon 4 allele (epsilon 4- 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 epsilon 4- AD was younger (P = .005, Student t test) and had an earlier age of onset (P = .005) than the group with epsilon 4+ 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,F-48 = 0.06; P = .81). However, contrary to hypothesis, significantly greater parietal rCBF asymmetry was seen in patients with epsilon 4- AD (mean +/- SD, 9.7% +/- 5.5%) than those with epsilon 4+ AD (6.3% +/- 4.7%; F-1,F-50 = 5.89; P = .02; analysis of variance). When number of epsilon 4 allele copies was considered, this effect appeared to accrue primarily from a difference between patients with 0 and with 2 epsilon 4 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 epsilon 4- AD than in epsilon 4+ AD. Lack of the epsilon 4 allele may be associated with other (as yet undiscovered) genetic or environmental risk factors, which confer greater neuropathological asymmetry.