Expression of cellular prion protein in the frontal and occipital lobe in Alzheimer's disease, diffuse Lewy body disease, and in normal brain: an immunohistochemical study.
Cellular prion protein (PrP(c)) is a glycoprotein expressed at low to moderate levels within the nervous system. Recent studies suggest that PrP(c) may possess neuroprotective functions and that its expression is upregulated in certain neurodegenerative disorders. We investigated whether PrP(c) expression is altered in the frontal and occipital cortex in two well-characterized neurodegenerative disorders--Alzheimer's disease (AD) and diffuse Lewy body disease (DLBD)--compared with that in normal human brain using immunohistochemistry and computerized image analysis. The distribution of PrP(c) was further tested for correlation with glial reactivity. We found that PrP(c) was localized mainly in the gray matter (predominantly in neurons) and expressed at higher levels within the occipital cortex in the normal human brain. Image analysis revealed no significant variability in PrP(c) expression between DLBD and control cases. However, blood vessels within the white matter of DLBD cases showed immunoreactivity to PrP(c). By contrast, this protein was differentially expressed in the frontal and occipital cortex of AD cases; it was markedly overexpressed in the former and significantly reduced in the latter. Epitope specificity of antibodies appeared important when detecting PrP(c). The distribution of PrP(c) did not correlate with glial immunoreactivity. In conclusion, this study supports the proposal that regional changes in expression of PrP(c) may occur in certain neurodegenerative disorders such as AD, but not in other disorders such as DLBD.
Rezaie
Payam
P
Department of Biological Sciences, Faculty of Science, The Open University, Walton Hall, Milton Keynes MK7 6AA, United Kingdom. p.rezaie@open.ac.uk
Pontikis
Charlie C
CC
Hudson
Lance
L
Cairns
Nigel J
NJ
Lantos
Peter L
PL
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000939:Epitopes; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009457:Neuroglia / Q000378:metabolism; D009778:Occipital Lobe / Q000378:metabolism*; D018621:PrPC Proteins / Q000096:biosynthesis*; D012016:Reference Values
D000939:Epitopes; D018621:PrPC Proteins