This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kawai, M. Articles by Perry, G. Search for Related Content PubMed PubMed Citation Articles by Kawai, M. Articles by Perry, G.

American Journal of Pathology, Vol 140, 947-958, Copyright © 1992 by American Society for Investigative Pathology

REGULAR ARTICLES

Subcellular localization of amyloid precursor protein in senile plaques of Alzheimer's disease

M Kawai, P Cras, P Richey, M Tabaton, DE Lowery, PA Gonzalez-DeWhitt, BD Greenberg, P Gambetti and G Perry
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106-4901.

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.

This article has been cited by other articles:

				R. A. Nixon Autophagy, amyloidogenesis and Alzheimer disease J. Cell Sci., December 1, 2007; 120(23): 4081 - 4091. [Abstract] [Full Text] [PDF]

				A. L. Friedlich, J.-Y. Lee, T. van Groen, R. A. Cherny, I. Volitakis, T. B. Cole, R. D. Palmiter, J.-Y. Koh, and A. I. Bush Neuronal Zinc Exchange with the Blood Vessel Wall Promotes Cerebral Amyloid Angiopathy in an Animal Model of Alzheimer's Disease J. Neurosci., March 31, 2004; 24(13): 3453 - 3459. [Abstract] [Full Text] [PDF]