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Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease.
Am J Pathol 1994; 145(6):1472-84AJ

Abstract

Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complications. The epsilon 4 allele frequency was increased in SDLT (0.365) and AD (0.328) as compared with controls (0.147), PD (0.098), or Huntington's chorea (0.171). Coronary disease and vascular dementia were associated with marginally higher epsilon 4 allele frequencies than in controls. In PD, amyloid beta-protein accumulated to a greater extent in those cases possessing an epsilon 4 allele than in those without. Those PD cases with dementia were not distinguished from either controls or PD cases without dementia, whether tested biochemically or by apolipoprotein E genotype. It is the comparison of the results in AD and SDLT that yielded the most significant findings. There was a 1.8-fold excess of amyloid beta-protein in AD as compared with controls, and the levels in SDLT were intermediate between those in AD and controls. In contrast, AD was discriminated from both controls and SDLT by the substantial accumulation of paired helical filament tau and phosphorylated tau (both increased more than 20-fold as compared with controls). SDLT was nevertheless characterized by an increased epsilon 4 allele frequency in the absence of significant tau pathology (at least 10-fold less than that in AD). These findings indicate that tau processing is more specifically associated with AD than is amyloid beta-protein accumulation and that presence of the epsilon 4 allele is not an etiological factor that accounts for tau pathology.

Authors+Show Affiliations

Cambridge Brain Bank Laboratory, University of Cambridge Department of Psychiatry, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7992850

Citation

Harrington, C R., et al. "Influence of Apolipoprotein E Genotype On Senile Dementia of the Alzheimer and Lewy Body Types. Significance for Etiological Theories of Alzheimer's Disease." The American Journal of Pathology, vol. 145, no. 6, 1994, pp. 1472-84.
Harrington CR, Louwagie J, Rossau R, et al. Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease. Am J Pathol. 1994;145(6):1472-84.
Harrington, C. R., Louwagie, J., Rossau, R., Vanmechelen, E., Perry, R. H., Perry, E. K., ... Wischik, C. M. (1994). Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease. The American Journal of Pathology, 145(6), pp. 1472-84.
Harrington CR, et al. Influence of Apolipoprotein E Genotype On Senile Dementia of the Alzheimer and Lewy Body Types. Significance for Etiological Theories of Alzheimer's Disease. Am J Pathol. 1994;145(6):1472-84. PubMed PMID: 7992850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease. AU - Harrington,C R, AU - Louwagie,J, AU - Rossau,R, AU - Vanmechelen,E, AU - Perry,R H, AU - Perry,E K, AU - Xuereb,J H, AU - Roth,M, AU - Wischik,C M, PY - 1994/12/1/pubmed PY - 1994/12/1/medline PY - 1994/12/1/entrez SP - 1472 EP - 84 JF - The American journal of pathology JO - Am. J. Pathol. VL - 145 IS - 6 N2 - Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complications. The epsilon 4 allele frequency was increased in SDLT (0.365) and AD (0.328) as compared with controls (0.147), PD (0.098), or Huntington's chorea (0.171). Coronary disease and vascular dementia were associated with marginally higher epsilon 4 allele frequencies than in controls. In PD, amyloid beta-protein accumulated to a greater extent in those cases possessing an epsilon 4 allele than in those without. Those PD cases with dementia were not distinguished from either controls or PD cases without dementia, whether tested biochemically or by apolipoprotein E genotype. It is the comparison of the results in AD and SDLT that yielded the most significant findings. There was a 1.8-fold excess of amyloid beta-protein in AD as compared with controls, and the levels in SDLT were intermediate between those in AD and controls. In contrast, AD was discriminated from both controls and SDLT by the substantial accumulation of paired helical filament tau and phosphorylated tau (both increased more than 20-fold as compared with controls). SDLT was nevertheless characterized by an increased epsilon 4 allele frequency in the absence of significant tau pathology (at least 10-fold less than that in AD). These findings indicate that tau processing is more specifically associated with AD than is amyloid beta-protein accumulation and that presence of the epsilon 4 allele is not an etiological factor that accounts for tau pathology. SN - 0002-9440 UR - https://www.unboundmedicine.com/medline/citation/7992850/Influence_of_apolipoprotein_E_genotype_on_senile_dementia_of_the_Alzheimer_and_Lewy_body_types__Significance_for_etiological_theories_of_Alzheimer's_disease_ L2 - https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/7992850/ DB - PRIME DP - Unbound Medicine ER -