Prion protein expression in senile plaques in Alzheimer's disease.
Prion protein (PrPC) is a glycolipid-anchored cell membrane sialoglycoprotein that localises in presynaptic membranes. Since synapses are vulnerable to Alzheimer's disease (AD), the present study examines PrPC expression in senile plaques, one of the major structural abnormalities in AD, by single- and double-labelling immunohistochemistry. Punctate PrPC immunoreactivity is found in diffuse plaques, whereas isolated large coarse PrPC-positive granules reminiscent of dystrophic neurites are observed in neuritic plaques. Finally, PrPC deposition also occurs as dense filamentous and amorphous precipitates in amyloid cores of senile plaques, but not in the walls of blood vessels with amyloid angiopathy. In contrast to PrPC, betaA4-amyloid immunoreactivity is preserved and even enhanced following incubation of the tissue sections with proteinase K prior to immunohistochemistry, thus indicating no PrPC and betaA4-amyloid cross-reactivity in dense amyloid cores of senile plaques. Punctate PrPC deposition in diffuse plaques is similar to that of synaptophysin, a synaptic vesicle-associated protein, as already reported in other studies. Immunoprecipitation, electrophoresis and Western blot studies have shown that synaptophysin, amyloid precursor protein (APP) and betaA4 do not co-precipitate with PrP. These results suggest that synaptophysin, APP and betaA4 are likely not bound to PrP. PrPC accumulation in betaA4-amyloid dense cores may be the consequence of the release of PrP into the extracellular space. Whether PrPC accumulation in the extracellular space is the result of impaired endocytosis and subsequent hydrolysis in the endosomal compartment, in contrast to normal degradation of PrPC, resulting from or occurring in parallel to abnormal APP degradation, deserves further study.
Ferrer
I
I
Unitat de Neuropatologia, Servei d'Anatomia Patològica, Hospital Princeps d'Espanya, Spain. iferrer@sakma.es
Blanco
R
R
Carmona
M
M
Puig
B
B
Ribera
R
R
Rey
M J
MJ
Ribalta
T
T
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D058225:Plaque, Amyloid / Q000473:pathology*; D018621:PrPC Proteins / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018621:PrPC Proteins; D016708:Synaptophysin