Longitudinal SPECT study in Alzheimer's disease: relation to apolipoprotein E polymorphism.
OBJECTIVE
In mild Alzheimer's disease, SPECT imaging of regional cerebral blood flow has highlighted deficits in the posterior association cortex, and later in the disease process, the deficit spreads to involve the frontal cortex. The sigma4 allele of apolipoprotein E is a risk factor for Alzheimer's disease. The effect of apolipoprotein E polymorphism on cerebral perfusion was studied. The hypothesis was that those patients with Alzheimer's disease who carry the sigma4 allele would have more severe cerebral hypoperfusion.


METHODS
Thirty one patients with Alzheimer's disease and eight age and sex matched control subjects were examined in a three year longitudinal study. Patients with Alzheimer's disease were divided into subgroups according to their number of sigma4 alleles. Regional cerebral blood flow ratios referred to the cerebellum were examined by 99mTc-HMPAO SPECT. Apolipoprotein E genotypes were determined by digestion of polymerase chain reaction products with the restriction enzyme Hha1.


RESULTS
All patients with Alzheimer's disease had bilateral temporoparietal hypoperfusion compared with control subjects. The two sigma4 allele subgroups had the lowest ratios at the baseline assessment in the parietal and occipital cortices, and at the follow up in the temporal, parietal, and occipital cortices. They had the highest reduction in percentage terms in the temporal and occipital cortices compared with the other subgroups. However, the global clinical severity did not differ at the baseline or follow up examinations between the subgroups.


CONCLUSIONS
Apolipoprotein E polymorphism is involved in the pathogenesis and heterogeneity of Alzheimer's disease as the most severe cerebral hypoperfusion was found in the sigma4 allele subgroups. This might have implications for therapeutic approaches in Alzheimer's disease.
Lehtovirta
M
M
Department of Neurology, Kuopio University Hospital and University of Kuopio, Finland.
Kuikka
J
J
Helisalmi
S
S
Hartikainen
P
P
Mannermaa
A
A
Ryynänen
M
M
Riekkinen PSr
Soininen
H
H
D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D019275:Radiopharmaceuticals; D012039:Regional Blood Flow / Q000502:physiology; D012720:Severity of Illness Index; D019690:Technetium Tc 99m Exametazime; D015899:Tomography, Emission-Computed, Single-Photon
D001057:Apolipoproteins E; D019275:Radiopharmaceuticals; D019690:Technetium Tc 99m Exametazime