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Differential distribution of amyloid protein precursor immunoreactivity in the rat brain studied by using five different antibodies
Author(s) -
Beeson James G.,
Shelton Earl R.,
Chan Hardy W.,
Gage Fred H.
Publication year - 1994
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.903420109
Subject(s) - senile plaques , biology , antibody , amyloid precursor protein , western blot , microbiology and biotechnology , amyloid (mycology) , peptide sequence , amino acid , alzheimer's disease , pathology , biochemistry , immunology , gene , disease , medicine , botany
The β‐amyloid or A4 protein is found deposited in neuritic plaques and neurofibrillary tangles in Alzheimer's disease (AD) affected brains and in the brains of adults with Down's Syndrome. The precursor to this 42 amino acid protein is the 695 amino acid long amyloid protein precursor (APP‐695). Two additional APP species, APP‐751 and APP‐770, each contain a 56‐amino‐acid insert sequence that is analogous to Kunitz protease inhibitors. APP mRNA is widely distributed in both the human and rat brain, although the adult rat does not develop mature amyloid pathology. In this study we used antibodies against the N‐terminus, junction site (unique to APP‐695) insert sequence (unique to APP‐751,‐770), A4 region, and C‐terminus of APP to immunolabel sections from throughout the young adult rat brain. From these results we constructed maps of the staining pattern of each antibody. We found that APP is widely distributed throughout the brain, that labelling is predominantly neuronal in character, and that there is marked variation among the antibodies in the extent of labelling, the particular cell populations stained, and the structures labelled within individual cells. The differential staining patterns observed with the five different antibodies suggest that the way APP is processed differs from one region to another and within different compartments in the cell. The specificity of the antibodies was established by Western blot analysis, in which APP species of approximately 95 and 110 kD were found. Our findings on the distribution of APP provide a foundation for further investigations into the normal role of APP and the pathogenesis of AD. © 1994 Wiley‐Liss, Inc.