Apolipoprotein E pathology in vascular dementia.
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.
Department of Biological Sciences, Boise State University Boise, ID 83725, USA.
Troy T
TT
Rohn
Department of Biological Sciences, Boise State University Boise, ID 83725, USA.
Ryan J
RJ
Day
Department of Biological Sciences, Boise State University Boise, ID 83725, USA.
Colin B
CB
Sheffield
Institute for Memory Impairments and Neurological Disorders, UC Irvine Irvine, CA 92697, USA.
Alexander J
AJ
Rajic
Institute for Memory Impairments and Neurological Disorders, UC Irvine Irvine, CA 92697, USA.
Wayne W
WW
Poon
D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000378:metabolism*; D015140:Dementia, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*
D001057:Apolipoproteins E
PHF-1; Vascular dementia; apoE; apolipoprotein E; astrocytes; immunohistochemistry; neurofibrillary tangles; plaques