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Neurology 1999;53:1825
© 1999 American Academy of Neurology
Articles

APOE-{epsilon}4 is associated with less frontal and more medial temporal lobe atrophy in AD

C. Geroldi, MD, M. Pihlajamäki, MD, M. P. Laakso, MD, PhD, C. DeCarli, MD, A. Beltramello, MD, A. Bianchetti, MD, H. Soininen, MD, PhD, M. Trabucchi, MD and G. B. Frisoni, MD

From the IRCCS San Giovanni di Dio–FBF (Drs. Geroldi, Bianchetti, Trabucchi, and Frisoni), Brescia, Italy; the Departments of Neurology (Drs. Pihlajamäki, Laakso, and Soininen) and Clinical Radiology (Dr. Laakso), Kuopio University Hospital, Kuopio, Finland; the Alzheimer’s Disease Center (Dr. DeCarli), Kansas University Medical Center, Kansas City, KS; and the Institute of Radiology (Dr. Beltramello), University of Verona, Ospedale Borgo Roma, Verona, Italy.

Address correspondence and reprint requests to Dr. Giovanni B. Frisoni, Alzheimer’s Disease Unit, IRCCS San Giovanni di Dio–FBF, via Pilastroni 4, 25123 Brescia, Italy.

OBJECTIVE: To test the hypothesis that the {epsilon}4 allele of APOE is associated with a region-specific pattern of brain atrophy in AD.

METHODS: Volumes of the hippocampi, entorhinal cortices, and anterior temporal and frontal lobes were measured in 28 mild to moderate AD patients and 30 controls using MRI. Within the AD group, 14 patients were noncarriers (-/-), 9 were heterozygous ({epsilon}4/-), and 5 were homozygous ({epsilon}4/4) for the {epsilon}4 allele. Dementia severity was similar across the three AD groups.

RESULTS: Smaller volumes were found with increasing dose of the {epsilon}4 allele in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients. When compared with controls, the volume loss in the right and left temporal regions ranged from -15.3 to -22.7% in the -/- AD group, from -26.2 to -36.0% in the {epsilon}4/- group, and from -24.0 to -48.0% in the {epsilon}4/4 group (p < 0.0005). In contrast, larger volumes were found in the frontal lobes with increasing {epsilon}4 gene dose. When compared with controls, volume differences of the right frontal lobe were -11.8% in the -/- AD group, -8.5 in the {epsilon}4/- group, and -1.4% in the {epsilon}4/4 group (p = 0.03).

CONCLUSIONS: We found smaller volumes in the temporal lobe regions but larger volumes in the frontal lobes with increasing APOE-{epsilon}4 gene dose in AD patients. These data suggest a region-specific biological effect of the {epsilon}4 allele in the brains of AD patients.

Key words: Apolipoprotein E—AD—Hippocampus—Entorhinal cortex—Temporal lobe—Frontal lobe—MRI.




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