Identification of N-terminally truncated pyroglutamate amyloid-β in cholesterol-enriched diet-fed rabbit and AD brain.

Abstract

The main amyloid-β peptide (Aβ) variants detected in the human brain are Aβ1-40 and Aβ1-42; however, a significant proportion of Aβ in Alzheimer's disease (AD) brain also consists of N-terminal truncated/modified species. AβN3(pE), Aβ peptide bearing amino-terminal pyroglutamate at position 3, has been demonstrated to be a major N-truncated/modified constituent of intracellular, extracellular, and vascular Aβ 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 Aβ 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 AβN3(pE) in blood vessels in cholesterol-enriched diet-fed rabbit brain. In addition, we detected AβN3(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 Aβ peptides in a suitable non-transgenic animal model.

• Authors: Roxanna Perez-Garmendia, Luis Fernando Hernandez-Zimbron, Miguel Angel Morales, José Luna-Muñoz, Raul Mena, Miriam Nava-Catorce, Gonzalo Acero, Vitaly Vasilevko, Amparo Viramontes-Pintos, David H Cribbs, Goar Gevorkian
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 39 Issue 2 Pg. 441-55 ( 2014) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 24240639 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• A N11(pE) peptide
• A N3(pE) peptide
• Amyloid beta-Peptides
• Antibodies
• Cholesterol, Dietary
• Peptide Fragments
• amyloid beta-protein (1-42)

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (metabolism)
• Amyloid beta-Peptides (metabolism)
• Animals
• Antibodies (metabolism)
• Astrocytes (metabolism)
• Brain (blood supply, metabolism)
• Cerebral Cortex (blood supply, metabolism)
• Cholesterol, Dietary (administration & dosage)
• Extracellular Space (metabolism)
• Hippocampus (blood supply, metabolism)
• Humans
• Intracellular Space (metabolism)
• Male
• Mice
• Mice, Transgenic
• Neurons (metabolism)
• Peptide Fragments (metabolism)
• Rabbits