Beta protein immunoreactivity is found in the majority of neurofibrillary tangles of Alzheimer's disease.
The presence of dystrophic neurites in most extracellular neurofibrillary tangles (E-NFT) suggests a factor promoting neurite growth in E-NFT. Although the beta-protein detected in E-NFT may fill that role, reports that only 2-10% of E-NFT contain beta-protein whereas 80-100% contain dystrophic neurites suggested that beta-protein does not play an important role. In this study, the authors used two antisera and one monoclonal antibody to beta-protein to establish the effects of tissue preparation and formic acid enhancement on the detection of beta-protein in E-NFT. We found that beta-protein epitopes in E-NFT are sensitive to formaldehyde fixation and are best enhanced by 50% formic acid, whereas beta-protein in senile plaques is best enhanced at higher formic acid concentrations. After treatment with 50% formic acid, beta-protein was found in all E-NFT. Interestingly, after treatment with 10% formic acid, half of intraneuronal-NFT (I-NFT) also contained beta-protein immunoreactivity. The finding that beta-protein immunoreactivity in senile plaques, E-NFT and I-NFT is increased at different formic acid concentrations suggests that beta-protein in each location is in a different conformation. In contrast, no beta-protein immunoreactivity could be found in E-NFT of the brain stem, an area in which dystrophic neurites do not infiltrate E-NFT. These findings indicate a correlation between neuritic infiltration and presence of beta-protein in E-NFT and suggests the two are linked in Alzheimer's disease for E-NFT as well as senile plaques.
Perry
G
G
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106-4901.
Cras
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P
Siedlak
S L
SL
Tabaton
M
M
Kawai
M
M
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000911:Antibodies, Monoclonal; D006624:Hippocampus / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D007124:Immunoenzyme Techniques; D016874:Neurofibrillary Tangles / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal