A severe loss of choline acetyltransferase in the frontal cortex of Alzheimer patients carrying apolipoprotein ε4 allele

We measured the activities of choline acetyltransferase (ChAT) in the post mortem frontal cortex in 32 Alzheimer's disease (AD) patients with different apolipoprotein E (apoE) genotypes. The ChAT values were significantly lower for the AD patients with 2 e4 alleles than for those with 0 e4 (ANOVA, 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 per min, ANOVA, P < 0.05. However, the AD patients carrying the e4 allele were significantly younger than those with 0 e4 allele. The study indicates that AD patients carrying the e4 allele have a more severe cholinergic deficit than the AD patients without the e4 allele.

[1]  Thomas Wisniewski,et al.  Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid , 1992, Neuroscience Letters.

[2]  B. Hyman,et al.  Apolipoprotein E in sporadic Alzheimer's disease: Allelic variation and receptor interactions , 1993, Neuron.

[3]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[4]  B. Tycko,et al.  The apolipoprotein ε4 allele in patients with Alzheimer's disease , 1993, Annals of neurology.

[5]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[6]  A. D. Roses,et al.  Association of apolipoprotein E allele €4 with late-onset familial and sporadic Alzheimer’s disease , 2006 .

[7]  L. Iversen,et al.  Neurochemical characteristics of early and late onset types of Alzheimer's disease. , 1984, British medical journal.

[8]  C. Mathew,et al.  Blot hybridisation analysis of genomic DNA. , 1984, Journal of medical genetics.

[9]  J. Poirier Apolipoprotein E in animal models of CNS injury and in alzheimer's disease , 1994, Trends in Neurosciences.

[10]  H. Soininen,et al.  Slowing of electroencephalogram and choline acetyltransferase activity in post mortem frontal cortex in definite Alzheimer's disease , 1992, Neuroscience.

[11]  Margaret A. Pericak-Vance,et al.  Hypothesis: Microtubule Instability and Paired Helical Filament Formation in the Alzheimer Disease Brain Are Related to Apolipoprotein E Genotype , 1994, Experimental Neurology.

[12]  E. Otomo,et al.  Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease , 1991, Brain Research.

[13]  M. Ashburner A Laboratory manual , 1989 .

[14]  E. Perry The cholinergic hypothesis--ten years on. , 1986, British medical bulletin.

[15]  F. Fonnum,et al.  A rapid radiochemical method for the determination of choline acetyltransferase , 1975, Journal of neurochemistry.

[16]  D. T. Vernier,et al.  Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. , 1990, Journal of lipid research.

[17]  S. M. Sumi,et al.  Alzheimer's disease: Choline acetyltransferase activity in brain tissue from clinical and pathological subgroups , 1983, Annals of neurology.

[18]  M. Pericak-Vance,et al.  Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[19]  T. Teramoto,et al.  Determination by PCR-RFLP of apo E genotype in a Japanese population. , 1993, The Journal of laboratory and clinical medicine.

[20]  R. Wurtman Choline metabolism as a basis for the selective vulnerability of cholinergic neurons , 1992, Trends in Neurosciences.

[21]  S. M. Sumi,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1991, Neurology.