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Absence of an Apolipoprotein E 4 Allele Is Associated With Increased Parietal Regional Cerebral Blood Flow Asymmetry in Alzheimer Disease

Christopher H. van Dyck, MD; Joel Gelernter, MD; Martha G. MacAvoy, PhD; Robert A. Avery, MA; Marc Criden, MA; Olivia Okereke, MD; Pradeep Varma, MD; John P. Seibyl, MD; Paul B. Hoffer, MD

Arch Neurol. 1998;55:1460-1466.

Background  The apolipoprotein E (Apo E) 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 4 allele on regional cerebral blood flow (rCBF) and metabolism in patients with probable AD.

Objective  To determine whether the Apo E 4 allele is associated with parietal rCBF abnormalities and asymmetries in patients with probable AD.

Patients and Methods  Thirty patients with AD with the 4 allele (4+ AD), 22 patients with AD without the 4 allele (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 4- AD was younger (P=.005, Student t test) and had an earlier age of onset (P=.005) than the group with 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_1,48=0.06; P =.81). However, contrary to hypothesis, significantly greater parietal rCBF asymmetry was seen in patients with 4- AD (mean±SD, 9.7%±5.5%) than those with 4+ AD (6.3%±4.7%; F_1,50=5.89; P =.02; analysis of variance). When number of 4 allele copies was considered, this effect appeared to accrue primarily from a difference between patients with 0 and with 2 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 4- AD than in 4+ AD. Lack of the 4 allele may be associated with other (as yet undiscovered) genetic or environmental risk factors, which confer greater neuropathological asymmetry.

From the Alzheimer's Disease Research Unit (Drs van Dyck, MacAvoy, and Okereke and Mssrs Avery and Criden) and the Division of Molecular Psychiatry (Dr Gelernter), Department of Psychiatry, and the Department of Diagnostic Radiology (Drs Varma, Seibyl, and Hoffer), Yale University School of Medicine, New Haven, Conn.

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