Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease

Topic: Brain proteins, microglia and lab models

Plain-language summary

These two subjects, both homozygous for the APOE-epsilon4 allele, were primarily diagnosed as having Creutzfeldt-Jakob disease and Pick's disease in the absence of significant neocortical amyloid deposition. More remarkably, the epsilon4 allele frequency was highly associated with AD subjects exhibiting lobar or intracerebral hemorrhage, all of whom had advanced CAA. We observed that 36% of the AD subjects had concomitant cerebrovascular pathology resulting from single infarcts, multiple microinfarcts, ischemic white matter lesions, or petechial hemorrhages. Although the difference in APOE genotype distribution between subjects with and without cerebrovascular lesions did not reach statistical significance, we did note that the frequency of the epsilon4 allele was significantly higher in subjects with such pathology as compared with those without. However, we found no evidence to suggest that the acquisition of an APOE-epsilon4 allele or one of the alleles, epsilon2 or epsilon3, was a factor in the occurrence of atherosclerosis localized in the basal surface arteries. Our results suggest that the APOE-epsilon4 allele is a significant factor in the development of CAA in AD and reveal the possibility that APOE is an independent factor in CAA and other vascular abnormalities associated with AD.

@article{premkumar1996-8669492,
  author  = {Premkumar, D. R. and Cohen, D. L. and Hedera, P. and Friedland, R. P. and Kalaria, R. N.},
  title   = {{Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease}},
  journal = {The American journal of pathology},
  year    = {1996},
  pmid    = {8669492}
}

Key findings

• These two subjects, both homozygous for the APOE-epsilon4 allele, were primarily diagnosed as having Creutzfeldt-Jakob disease and Pick's disease in the absence of significant neocortical amyloid deposition.
• More remarkably, the epsilon4 allele frequency was highly associated with AD subjects exhibiting lobar or intracerebral hemorrhage, all of whom had advanced CAA.
• We observed that 36% of the AD subjects had concomitant cerebrovascular pathology resulting from single infarcts, multiple microinfarcts, ischemic white matter lesions, or petechial hemorrhages.
• Although the difference in APOE genotype distribution between subjects with and without cerebrovascular lesions did not reach statistical significance, we did note that the frequency of the epsilon4 allele was significantly higher in subjects with such pathology as compared with those without.
• However, we found no evidence to suggest that the acquisition of an APOE-epsilon4 allele or one of the alleles, epsilon2 or epsilon3, was a factor in the occurrence of atherosclerosis localized in the basal surface arteries.

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Study details

• Evidence strengthLow

Read the original

• PubMed: 8669492
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