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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.

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


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.


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

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