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P4‐020: Hyperphosphorylation along the C‐terminal of tau protein is associated with PHF assembly resulting from truncation at Glu‐391, in AlzheimerÂś disease
Author(s) -
LunaMuñoz José,
Flores Paola,
Zamudio Sergio Zamudio,
De la Cruz De la Cruz Fidel,
Harrington Charles R,
Wischik Claude M.,
López Raúl Mena
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2040
Subject(s) - tau protein , hyperphosphorylation , tangle , chemistry , microbiology and biotechnology , extracellular , monoclonal antibody , neurofibrillary tangle , antibody , phosphorylation , alzheimer's disease , biophysics , pathology , senile plaques , biology , biochemistry , medicine , disease , immunology , mathematics , pure mathematics
Background: Hyperphosphorylated and truncated species of tau molecule are characteristically found in the paired helical filaments (PHF) which are found in Alzheimer’s diseased brains. A causal relationship between those two events has not been determined yet. After the neuronal death, the intracellular neurofibrillary tangle (NFT) is eventually released into the extracellular space becoming a ghost tangle. This structure is characteristically identified by themonoclonal antibody 423 which was raised against a fragment of tau protein which carries a C-terminal truncation at Glu-391 (Novak et al. Embo J, 1993. 12: 365-70). This truncated tau protein represents the so called PHF-core, which is characteristically stable and highly insoluble. By in vitro studies, it has demonstrated that the PHF core is highly toxic by inducing apoptosis. Objective. To determine the relationships between C-end hyperphosphorylation and Glu391 truncation at early stages of PHF assembly. Methods: This study was based on double and triple immunolabelling using 423, S396, S400, S404, S409 AD2, S422, counterstained with Thiazin red (TR) (Acta Neuropathol, 1996. 91: 633-41). Slides were analized using confocal microscopy. Results: The immunoreactivity of all phospho-dependent tau antibodies, excepting S422, was found colocalizing with TR in the forms of beads or small tangles in the proximal neuronal processes As expected, E-NFTwere detected by 423. Interestingly, the phospho-dependent tau marker, S396, was also found in the latter structures. Conclusions: This study suggests that the phosphorylation tau protein processing results as a consequence of the appearance of the PHF core. In general, this confocal analysis indicates that hyperphosphorylation processing along the C-portion of tau protein is a protective response to toxicity produced by the appearance of the PHF core fragments, whose exposure leads to tau protein assembly into PHF.