Author/Editor		Praprotnik, Darja
Title		Immunocytochemical properties of filaments in the dystrophic neurites of Alzheimer's disease
Translated title		Imunocitokemične lastnosti filamentov v distrofičnih nevritih pri Alzheimerjevi bolezni
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 65, št. 2
Publication year		1996
Volume		str. 61-5
Language		eng
Abstract		Background. Senile plaques of Alzheimer's disease are comprised of fibrillary deposits of amyloid beta in the centre, surounded by degenerating or dystrophic neurites. The dystrophic neurites contain abnormal paired helical filaments, straight filaments and various vesicles. The relationship between the dystrophic neurites and the extracellular amyloid beta deposits is not clarified. It has been shown, that the abnormal filaments in the dystrophic neurites contain protein tau, ubiquitin and neurofilaments. The dystrophic neurites also contain epitopes of beta-precursor protein and-or amyloid beta and the components of extracellular matrix. In this study we tried to find out, if beta-precursor protein-amyloid beta epitopes are present on tau-positive filaments of dystrophic neurites. Material and methods. In the study autopsy tissue from brain cortex of four patients fulfilling the internationally confirmed criteria for the diagnosis of Alzheimer's disease were included. Light and electron double immunostaining methods were performed. We used antisera specific for protein tau, ubiquitin, beta-precursor protein-amyloid beta, synaptophysin and glial fibrillary acidic protein GFAP. Results. The dystrophic neurites often contained protein tau, ubiquitin, synaptophysin and beta-precursor protein-amyloid beta epitopes, but not always simultaneously. Electron microscopic double immunogold staining methods showed consistent presence of protein tau and ubiquitin on paired helical filaments and straight filaments. These filaments often showed presence of beta-precursor protein-amyloid beta epitopes, which are also present on granular senile plaques outside the dystrophic neurites contained only beta-precursor protein-amyloid beta epitopes. GFAP was not present inside the plaques. Conclusion.(trunc.)
Summary		Izhodišča. Senilne plake pri Alzheimerjevi bolezni sestavljajo osrednji fibrilarni depoziti amiloida beta, v okolici pa so nakopičeni propadajoči oziroma distrofični nevriti, ki vsebujejo nenormalne zvite filamente in ravne filamente ter različne vezikule. Amiloid beta nastane kot posledica nenormalnega cepljenja večje transmembranske molekule beta-prekurzorskega proteina, katere fiziološka vloga ni znana. Patogenetski mehanizem, ki privede do odlaganja amiloida beta v izvenceličnem prostoru, ni pojasnjen. Z imunohistokemičnimi metodami so prikazali, da osrednji deli senilnih plakov sicer vsebujejo amiloid beta kot osnovno sestavino, poleg tega pa vsebujejo tudi epitope beta-prekurzorskega proteina, ki se nahajajo izven predela, ki zajema aminokislinsko zaporedje amiloida beta, razne encime in njihove inhibitorje ter sestavine izvenceličnega matriksa. Odnos med distrofičnimi nevriti in izvenceličnimi fibrilarnimi amiloidnimi depoziti ni pojasnjen. Nenormalni parni zviti filamenti in ravni filamenti, ki se pri Alzheimerjevi bolezni pojavijo v perikarionih živčnih celic in distrofičnih nevritih, nastanejo kot posledica preoblikovanja normalnega citoskeleta. Ti filamenti so odporni na delovanje proteolitičnih encimov in po odmrtju živčnih celic ostanejo v izvenceličnem prostoru. Poznano je, da nenormalni filamenti v distrofičih nevritih vsebujejo epitope proteina tau, ubikvitina in nevrofilamentov. Poleg teh sestavin pa tudi distrofični nevriti vsebujejo epitope beta-prekurzorskega proteina oziroma amiloida beta in sestavine ekstracelularnega matriksa.
Descriptors		ALZHEIMER'S DISEASE CEREBRAL CORTEX IMMUNOHISTOCHEMISTRY AMYLOID BETA-PROTEIN