Premium
Monoclonal Antibodies Against the Human Metalloprotease EC 3.4.24.15 Label Neurofibrillary Tangles in Alzheimer's Disease Brain
Author(s) -
Conn Kelly J.,
Pietropaolo Michael,
Ju ShyrTe,
Abraham Carmela R.
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66052011.x
Subject(s) - senile plaques , biochemistry of alzheimer's disease , amyloid (mycology) , alzheimer's disease , amyloid precursor protein , p3 peptide , neurofibrillary tangle , bace1 as , chemistry , biochemistry , monoclonal antibody , proteases , microbiology and biotechnology , pathology , biology , antibody , immunology , medicine , enzyme , inorganic chemistry , disease
Alzheimer's disease is characterized neuropathologically by the presence of neuritic and amyloid plaques, vascular amyloid, and neurofibrillary tangles in specific brain areas. The main constituent of amyloid deposits is amyloid β protein, a 40–42 amino acid proteolytic product of the amyloid β‐precursor protein. In our search for proteases that can generate the N‐terminus of amyloid β protein (β‐secretases), we discovered a thiol‐dependent metalloprotease that was identified, by peptide sequencing, as metalloendopeptidase EC 3.4.24.15. In vitro, the metalloprotease cleaves the methionine‐aspartic acid bond in a 10 amino acid synthetic peptide, indicating that it could generate the N‐terminus of amyloid β protein, and generates amyloidogenic fragments from full‐length recombinant amyloid β‐precursor protein. Mouse monoclonal antibodies produced against a unique synthetic peptide from the metalloprotease labeled various monkey tissues as detected by western blots and immunohistochemistry. Unexpectedly, two monoclonal antibodies, IVD6 and IIIF3, immunolabeled strongly intracellular neurofibrillary tangles, neurites of senile plaques, and neuropil threads, but not “ghost” tangles or amyloid in sections taken from Alzheimer's disease brain. This finding provides further evidence for the metalloprotease's relevance to Alzheimer's disease pathology, although the connection between tangle staining and the formation of amyloid β protein remains to be elucidated.