title: Aging, cortical injury and Alzheimer's disease-like pathology in the guinea pig brain.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized histopathologically by the abnormal deposition of the proteins amyloid-beta (Aβ) and tau. A major issue for AD research is the lack of an animal model that accurately replicates the human disease, thus making it difficult to investigate potential risk factors for AD such as head injury. Furthermore, as age remains the strongest risk factor for most of the AD cases, transgenic models in which mutant human genes are expressed throughout the life span of the animal provide only limited insight into age-related factors in disease development. Guinea pigs (Cavia porcellus) are of interest in AD research because they have a similar Aβ sequence to humans and thus may present a useful non-transgenic animal model of AD. Brains from guinea pigs aged 3-48 months were examined to determine the presence of age-associated AD-like pathology. In addition, fluid percussion-induced brain injury was performed to characterize mechanisms underlying the association between AD risk and head injury. No statistically significant changes were detected in the overall response to aging, although we did observe some region-specific changes. Diffuse deposits of Aβ were found in the hippocampal region of the oldest animals and alterations in amyloid precursor protein processing and tau immunoreactivity were observed with age. Brain injury resulted in a strong and sustained increase in amyloid precursor protein and tau immunoreactivity without Aβ deposition, over 7 days. Guinea pigs may therefore provide a useful model for investigating the influence of environmental and non-genetic risk factors on the pathogenesis of AD.
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia; School of Psychiatry and Clinical Neuroscience, The University of Western Australia, Crawley, Western Australia, Australia; The McCusker Foundation for Alzheimer's Disease Research Inc, Nedlands, Western Australia, Australia. Electronic address: kristyn.bates@uwa.edu.au.
authors.forename: Kristyn
authors.initials: K
authors.lastname: Bates
authors.affiliation: School of Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: Vink
authors.affiliation: School of Psychiatry and Clinical Neuroscience, The University of Western Australia, Crawley, Western Australia, Australia; The McCusker Foundation for Alzheimer's Disease Research Inc, Nedlands, Western Australia, Australia; School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
authors.forename: Ralph
authors.initials: R
authors.lastname: Martins
authors.affiliation: School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Harvey
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001930:Brain Injuries / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D008297:Male; D012307:Risk Factors; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016875:tau Proteins
keywords: Aging; Alzheimer's disease; Amyloid-beta; Head injury