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H. Soininen*, M. Lehtovirta, S. Helisalmi, K. Linnaranta, O. Heinonen, O. Kosunen, L. Palj_rvi, and P.J. Riekkinen Sr. Depts Neurology, Pathology, Unit of Clinical Genetics, University Hospital, A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland

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Apolipoprotein E (apoE) allele e4 is a risk factor for Alzheimer's disease (AD). We measured the activities of choline acetyltransferase (ChAT) in the post mortem frontal cortex in 32 patients fulfilling the CERAD criteria of definite AD with different apoE genotypes and CSF acetylcholinesterase (AChE) activity in 57 patients with mild to moderate AD and with different apoE genotypes. The ChAT activities were significantly reduced in the frontal cortex of all AD subgroups with 2, 1, or 0 e4 allele compared to controls (p<0.0001). The ChAT activities were also significantly lower for the AD patients with 2 e4 alleles than for those with 0 e4 allele (Duncan p<0.05). The ChAT activities of AD patients carrying 2 or 1 e4 alleles and those without the e4 allele also differed significantly: 16.3±15.2 versus 30.5±20.6 pmol / mg protein / min, ANOVA, p<0.05. The scores of plaques or tangles did not differ across the AD subgroups. The CSF AChE activities of the whole AD group did not differ from those of controls. However, analysis of variance over the AD subgroups with 2, 1, and no e4 alleles and controls showed significant differences (p<0.0001); the AD patients with 2 e4 alleles had higher AChE activities than controls and AD patients with 1 or no e4, and also the AD patients carrying 1 e4 allele had higher AChE activities than the AD patients without the e4 allele. The study suggests that the cholinergic metabolism is altered in AD patients in proportion to the number of apoE e4 alleles. The AD patients carrying the e4 allele had a more severe cholinergic deficit in the frontal cortex than the AD patients without the e4 allele. The different degree of CSF AChE activity in relation to the number of e4 alleles might imply differences in AD patients' response to cholinesterase inhibitors.