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A quantitative analysis of cellular prion protein (PrP c ) expression in Alzheimer's disease (AD), diffuse Lewy body disease (DLBD) and in normal brain
Author(s) -
Pontikis C.,
Hudson L.,
Lantos P. L.,
Rezaie P.
Publication year - 2002
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1046/j.1365-2990.2002.39286_49.x
Subject(s) - neuropathology , pathology , lewy body , immunohistochemistry , alzheimer's disease , biology , microbiology and biotechnology , medicine , disease , dementia
Cellular prion protein (PrP c ) is a normal glycosyl phosphatidylinositol‐anchored protein expressed on a wide variety of cell types. Within the CNS, low levels of PrP c are particularly associated with neurons in normal healthy individuals. In contrast, a more pronounced expression of this protein may occur in certain neurodegenerative disorders (Esiri et al . Neuropath Appl Neurobiol 2000; 26 : 273; Voigtlander et al . Acta Neuropathol 2001; 101 : 417). Overexpression of PrP c has itself been reported to demonstrate neuropathology in transgenic mice (Westaway et al . Cell 1994; 76 : 117). The present study investigated whether prion protein is up‐regulated in two well‐characterized neurodegenerative disorders: Alzheimer's disease (AD) and diffuse Lewy body disease (DLBD). Material and methods: Frozen material (frontal and occipital cortex) from cases with AD ( n = 10), DLBD ( n = 10) and neuropathologically normal brain ( n = 10) were obtained from the MRC Brain Bank (Institute of Psychiatry, London), serially sectioned at 15–20 µm and immunoreacted in entire batches with four antisera to detect PrP c (3f4, sp40, 12f10 and F89/160.1.5) using the DAKO ABC method and DAB as chromogen. Sections from a case with Creutzfeldt‐Jakob disease served as positive controls. Negative controls included preincubating test sections with proteinase K/guanidinium thiocyanate/formic acid, omitting primary antibody or incubation with nonspecific IgG. Immunoreactivity within selected brain regions was analysed using OPTIMAS image analysis software (OPTIMAS Corp., USA) on duplicate sections, and data processed as percentage immunoreactivity per defined field, based on a constant threshold (von Eitzen et al . JNEN 1998; 57 : 246). The distribution of PrP c was further tested for correlation with glial reactivity (GFAP, PGM‐1). Results: PrP c expression was mainly localized to the grey matter and was higher in occipital than frontal cortex. PrP c did not colocalize with glial reactivity. Instead, expression within the grey matter appeared to associate with neurons. Expression did not vary significantly between DLBD and controls. However, regional variations in PrP c expression were noted in AD. Epitope specificity of antibodies was also important in detecting PrP c , and may relate to selective regional glycosylation patterns of this protein. Conclusion: This study indicates that changes in expression of PrP c occur in certain neurodegenerative disorders such as AD. Whether this is secondary to the disease or contributes towards pathology remains to be investigated.