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J Alzheimers Dis. 2014;39(2):441-55. doi: 10.3233/JAD-130590.

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

Author information

  • 1Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico (UNAM), Cuidad Universitaria, Mexico, DF, Mexico.
  • 2Brain Bank, National Laboratory of Experimental Services, CINVESTAV-IPN, Mexico, DF, Mexico.
  • 3Department of Neurosciences, CINVESTAV-IPN, Mexico, DF, Mexico.
  • 4Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA.
  • 5Institute for Memory Impairments and Neurological Disorders, University of California Irvine, Irvine, CA, USA Department of Neurology, University of California Irvine, Irvine, CA, USA.

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.

KEYWORDS:

Alzheimer's disease; amyloid-β; animal model; cholesterol-fed rabbit; pyroglutamate-modified amyloid

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