The apolipoprotein E (Apo E) ϵ4 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 ϵ4 allele on regional cerebral blood flow (rCBF) and metabolism in patients with probable AD.
To determine whether the Apo E ϵ4 allele is associated with parietal rCBF abnormalities and asymmetries in patients with probable AD.
Patients and Methods
Thirty patients with AD with the ϵ4 allele (ϵ4+ AD), 22 patients with AD without the ϵ4 allele (ϵ4− 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.
The group with ϵ4− AD was younger (P=.005, Student t test) and had an earlier age of onset (P=.005) than the group with ϵ4+ AD. Analysis of covariance revealed no significant difference in the parietal rCBF ratio, controlling for age of onset and Mini–Mental State Examination score (F1,48=0.06; P =.81). However, contrary to hypothesis, significantly greater parietal rCBF asymmetry was seen in patients with ϵ4− AD (mean±SD, 9.7%±5.5%) than those with ϵ4+ AD (6.3%±4.7%; F1,50=5.89; P =.02; analysis of variance). When number of ϵ4 allele copies was considered, this effect appeared to accrue primarily from a difference between patients with 0 and with 2 ϵ4 allele copies. An exploratory analysis of multiple cortical structures suggested that this asymmetry extended to additional regions (superior temporal) and to combined association cortex.
Greater parietal rCBF asymmetry is involved in ϵ4− AD than in ϵ4+ AD. Lack of the ϵ4 allele may be associated with other (as yet undiscovered) genetic or environmental risk factors, which confer greater neuropathological asymmetry.