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The Amyloid Precursor Protein of Alzheimer's Disease Localizes to Plaques on the Surfaces of Axoplasmic Organelles
Author(s) -
DeGiorgis Joseph Alan,
Scollins Brianne J,
Walsh Rylie B
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.762.17
Subject(s) - axoplasm , microtubule , organelle , axoplasmic transport , kinesin , microbiology and biotechnology , amyloid precursor protein , squid giant axon , axon , immunogold labelling , vesicle , chemistry , endosome , synaptic vesicle , biology , alzheimer's disease , biochemistry , ultrastructure , pathology , anatomy , medicine , intracellular , disease , membrane
Alzheimer disease afflicts an estimated 26 million individuals worldwide and its incidence is predicted to reach 100 million by 2050. This debilitating neurodegenerative disease is characterized by loss of long‐term memory, language degeneration, and cognitive impairment. Mutations in the amyloid precursor protein (APP) lead to heritable forms of this disorder, however, little is known about the wildtype function of APP or how mutations in APP lead to AD pathogenesis. Here, we set out to study the distribution of APP at the ultrastructural level in extruded axoplasm of the squid giant axon as well as in reconstituted axoplasmic organelle/microtubule complexes. By immunogold electron microscopy using a C‐terminal APP antibody, gold particles distribute to plaques on the surfaces of 100 nm vesicles in axoplasm. Many of these organelles are bound to microtubules and APP often localizes to the organelle/microtubule interface. In reconstituted organelle/microtubule complexes, APP remains integral to the organelle membrane. These organelles bind to the microtubules in the absence of ATP and we have previously shown that they have Kinesin‐3 on their surfaces. These vesicles also move to the plus ends of microtubules indicating that APP is a cargo or maybe directly involved in the transport process. This work was funded by the Rhode Island IDeA Network of Biomedical Research Excellence (INBRE).