Subcellular localization of amyloid precursor protein in senile plaques of Alzheimer's disease.
The authors have previously shown that amyloid precursor protein (APP) accumulates in neurites present in senile plaques of Alzheimer's disease (AD). In this ultrastructural immunocytochemical study, we describe the subcellular site of APP accumulation. Vibratome sections of glutaraldehyde-paraformaldehyde fixed hippocampi from five cases of AD were pretreated with methanol and immunostained with an antibody raised against recombinant APP 770 by using either indirect immunogold or peroxidase methods. Immunolabeling was localized in cell processes filled with amorphous, irregular-shaped materials, which were identified as dense bodies deformed by postmortem autolysis and methanol treatment, as well as multilamellar membranous bodies. Identification of these bodies was obtained with comparative ultrastructural examination of biopsy and autopsy tissue fixed with and without methanol treatment. These electron-dense organellae were positive for the lysosomal marker, acid phosphatase. At light microscopy, acid phosphatase and APP colocalized to the same cell processes in senile plaques. Many of those cell processes contained abnormal straight or paired helical filaments supporting their neuritic nature. These results suggest that APP accumulates in the lysosomal system of the dystrophic neurites present in senile plaques and are consistent with a neuronal origin of the APP forming the amyloid in senile plaques.
Kawai
M
M
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106-4901.
Cras
P
P
Richey
P
P
Tabaton
M
M
Lowery
D E
DE
Gonzalez-DeWhitt
P A
PA
Greenberg
B D
BD
Gambetti
P
P
Perry
G
G
D000135:Acid Phosphatase / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D000432:Methanol / Q000494:pharmacology; D008854:Microscopy, Electron; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D011180:Postmortem Changes; D013347:Subcellular Fractions / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins; D000135:Acid Phosphatase; D000432:Methanol