OBJECTIVES: 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. CONCLUSION: 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.
OBJECTIVES: 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. CONCLUSION: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.
Authors: R Mayeux; Y Stern; R Ottman; T K Tatemichi; M X Tang; G Maestre; C Ngai; B Tycko; H Ginsberg Journal: Ann Neurol Date: 1993-11 Impact factor: 10.422
Authors: H S Soininen; K Partanen; A Pitkänen; P Vainio; T Hänninen; M Hallikainen; K Koivisto; P J Riekkinen Journal: Neurology Date: 1994-09 Impact factor: 9.910
Authors: M Lehtovirta; M P Laakso; H Soininen; S Helisalmi; A Mannermaa; E L Helkala; K Partanen; M Ryynänen; P Vainio; P Hartikainen Journal: Neuroscience Date: 1995-07 Impact factor: 3.590
Authors: W J Strittmatter; K H Weisgraber; M Goedert; A M Saunders; D Huang; E H Corder; L M Dong; R Jakes; M J Alberts; J R Gilbert Journal: Exp Neurol Date: 1994-02 Impact factor: 5.330
Authors: E K Perry; V Haroutunian; K L Davis; R Levy; P Lantos; S Eagger; M Honavar; A Dean; M Griffiths; I G McKeith Journal: Neuroreport Date: 1994-03-21 Impact factor: 1.837
Authors: M Lehtovirta; S Helisalmi; A Mannermaa; H Soininen; K Koivisto; M Ryynänen; P Riekkinen Journal: Neurosci Lett Date: 1995-02-06 Impact factor: 3.046
Authors: G W Small; J C Mazziotta; M T Collins; L R Baxter; M E Phelps; M A Mandelkern; A Kaplan; A La Rue; C F Adamson; L Chang Journal: JAMA Date: 1995 Mar 22-29 Impact factor: 56.272
Authors: H Soininen; O Kosunen; S Helisalmi; A Mannermaa; L Paljärvi; S Talasniemi; M Ryynänen; P Riekkinen Journal: Neurosci Lett Date: 1995-03-03 Impact factor: 3.046
Authors: Timo Grimmer; Susanne Tholen; Behrooz H Yousefi; Panagiotis Alexopoulos; Annette Förschler; Hans Förstl; Gjermund Henriksen; William E Klunk; Chester A Mathis; Robert Perneczky; Christian Sorg; Alexander Kurz; Alexander Drzezga Journal: Biol Psychiatry Date: 2010-07-02 Impact factor: 13.382
Authors: David L McDonagh; Joseph P Mathew; Willam D White; Barbara Phillips-Bute; Daniel T Laskowitz; Mihai V Podgoreanu; Mark F Newman Journal: Anesthesiology Date: 2010-04 Impact factor: 7.892
Authors: L Mosconi; K Herholz; I Prohovnik; B Nacmias; M T R De Cristofaro; M Fayyaz; L Bracco; S Sorbi; A Pupi Journal: J Neurol Neurosurg Psychiatry Date: 2005-01 Impact factor: 10.154
Authors: S Cosentino; N Scarmeas; E Helzner; M M Glymour; J Brandt; M Albert; D Blacker; Y Stern Journal: Neurology Date: 2008-04-09 Impact factor: 9.910
Authors: Leon M Tai; Riya Thomas; Felecia M Marottoli; Kevin P Koster; Takahisa Kanekiyo; Alan W J Morris; Guojun Bu Journal: Acta Neuropathol Date: 2016-02-16 Impact factor: 17.088
Authors: L Mosconi; B Nacmias; S Sorbi; M T R De Cristofaro; M Fayazz; A Tedde; L Bracco; K Herholz; A Pupi Journal: J Neurol Neurosurg Psychiatry Date: 2004-03 Impact factor: 10.154