Apolipoprotein E pathology in vascular dementia

Int J Clin Exp Pathol. 2014 Feb 15;7(3):938-47. eCollection 2014.

Abstract

Vascular dementia (VaD) is the second most common form of dementia and is currently defined as a cerebral vessel vascular disease leading to ischemic episodes. Apolipoprotein E (apoE) gene polymorphism has been proposed as a risk factor for VaD, however, to date there are few documented post-mortem studies on apoE pathology in the VaD brain. To investigate a potential role for the apoE protein, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing an antibody that specifically detects the amino-terminal fragment of apoE. Application of this antibody, termed N-terminal, apoE cleavage fragment (nApoECF) revealed consistent labeling within neurofibrillary tangles (NFTs), blood vessels, and reactive astrocytes. Labeling occurred in VaD cases that had confirmed APOE genotypes of 3/3, 3/4, and 4/4, with respect to NFTs, staining of the nApoECF co-localized with PHF-1 and was predominantly localized to large, stellate neurons in layer II of the entorhinal cortex. Quantitative analysis indicated that approximately 38.4% of all identified NFTs contained the amino-terminal fragment of apoE. Collectively, these data support a role for the proteolytic cleavage of apoE in the VaD and support previous reports that APOE polymorphism is significantly associated with susceptibility in this disease.

Keywords: PHF-1; Vascular dementia; apoE; apolipoprotein E; astrocytes; immunohistochemistry; neurofibrillary tangles; plaques.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / metabolism*
  • Dementia, Vascular / metabolism
  • Dementia, Vascular / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Neurofibrillary Tangles / chemistry
  • Neurofibrillary Tangles / metabolism
  • Neurofibrillary Tangles / pathology*

Substances

  • Apolipoproteins E