Identification of N-Terminally Truncated Pyroglutamate Amyloid-beta in Cholesterol-Enriched Diet-Fed Rabbit and AD Brain
Por:
Perez-Garmendia R., Hernandez-Zimbron L.F., Morales M.A., Luna-Muñoz J., Mena R., Nava-Catorce M., Acero G., Vasilevko V., Viramontes-Pintos A., Cribbs D.H., Gevorkian G.
Publicada:
1 ene 2014
Resumen:
The main amyloid-beta peptide (A beta) variants detected in the human
brain are A beta(1-40) and A beta(1-42); however, a significant
proportion of A beta in Alzheimer's disease (AD) brain also consists of
N-terminal truncated/modified species. A beta N3(pE), A beta peptide
bearing amino-terminal pyroglutamate at position 3, has been
demonstrated to be a major N-truncated/modified constituent of
intracellular, extracellular, and vascular A beta deposits in AD and
Down syndrome brain tissue. It has been previously demonstrated that
rabbits fed a diet enriched in cholesterol and given water containing
trace copper levels developed AD-like pathology including intraneuronal
and extracellular A beta accumulation, tau hyperphosphorylation,
vascular inflammation, astrocytosis, microgliosis, reduced levels of
acetylcholine, as well as learning deficits and thus, may be used as a
non-transgenic animal model of sporadic AD. In the present study, we
have demonstrated for the first time the presence of A beta N3(pE) in
blood vessels in cholesterol-enriched diet-fed rabbit brain. In
addition, we detected A beta N3(pE) immunoreactivity in all postmortem
AD brain samples studied. We believe that our results are potentially
important for evaluation of novel therapeutic molecules/strategies
targeting A beta peptides in a suitable non-transgenic animal model.
Filiaciones:
Perez-Garmendia R.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF, Mexico
Hernandez-Zimbron L.F.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF, Mexico
Morales M.A.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF, Mexico
Luna-Muñoz J.:
Brain Bank, National Laboratory of Experimental Services, CINVESTAV-IPN, Mexico, DF, Mexico
Mena R.:
Department of Neurosciences, CINVESTAV-IPN, Mexico, DF, Mexico
Nava-Catorce M.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF, Mexico
Acero G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF, Mexico
Vasilevko V.:
Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, United States
Viramontes-Pintos A.:
Brain Bank, National Laboratory of Experimental Services, CINVESTAV-IPN, Mexico, DF, Mexico
Cribbs D.H.:
Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, United States
Department of Neurology, University of California Irvine, Irvine, CA, United States
Gevorkian G.:
Univ Nacl Autonoma Mexico, Inst Invest Biomed, Mexico City 04510, DF, Mexico
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