title: Amyloid Beta1-42 and the Phoshorylated Tau Threonine 231 in Brains of Aged Cynomolgus Monkeys (Macaca fascicularis).
abstract: Pathological hallmarks indicative of Alzheimer's disease (AD), which are the plaques of amyloid beta1-42 and neurofibrillary tangles, were found in brain of aged cynomolgus monkey. The aim of this study was to investigate if aged monkeys exhibiting spatial memory impairment and levels of biomarkers indicative of AD, had brain lesions similar to human patients suffering from senile dementia. Generating immunohistochemistry technique to biomarkers of amyloid beta1-42 and the phosphorylated tau 231, our study assessed the amyloidopathy, such as indicative to the senile plaques and cerebral amyloid angiopathy, and the tauopathy, to possible neurofibrillary tangles. Six aged monkeys were selected based on their spatial memory performance and profile of biomarkers of AD, divided equally to affected aged subject - with Memory-affected and low amyloid level, and aged with higher performance in memory and amyloid, as the age-matched subjects. Using immunohistochemistry, plaques of amyloid beta1-42 were observed in two out of three brains of aged subjects with memory impairment and biomarkers indicative of AD. The cerebral amyloid angiopathy was observed in both aged monkey groups, and unlike in the human, the amyloids were found to deposit in the small veins and capillaries. In one of the affected individuals, phosphorylated tau was positively stained intracellularly of the neurons, indicating a possibility of an early stage of the formation of tangles. These findings add to the body of evidence of the utility of the aged cynomolgus monkeys as a spontaneous model for Alzheimer-related disease.
authors.affiliation: Department of Experimental Medicine, Faculty of Health Science, University of Copenhagen , Copenhagen , Denmark ; Department of Anatomy, Physiology and Pharmacology, Faculty of Veterinary Medicine, Bogor Agricultural University , Bogor , Indonesia.
authors.forename: Huda Shalahudin
authors.initials: HS
authors.lastname: Darusman
authors.affiliation: Department of Neuroscience and Pharmacology, Faculty of Health Science, University of Copenhagen , Copenhagen , Denmark ; Center for Functionally Integrative Neuroscience, University of Aarhus , Aarhus , Denmark ; Department of Radiology and Radiological Science, Johns Hopkins University , Baltimore, MD , USA ; Department of Neurology and Neurosurgery, McGill University , Montréal, QC , Canada.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
authors.affiliation: Primate Research Center, Bogor Agricultural University , Bogor , Indonesia.
authors.forename: Dondin
authors.initials: D
authors.lastname: Sajuthi
authors.affiliation: Department of Experimental Medicine, Faculty of Health Science, University of Copenhagen , Copenhagen , Denmark ; Department of Veterinary Sciences, The University of Texas MD Anderson Cancer Center , Bastrop, TX , USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schapiro
authors.affiliation: Department of Experimental Medicine, Faculty of Health Science, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Otto
authors.initials: O
authors.lastname: Kalliokoski
authors.affiliation: Department of Pathology, Faculty of Veterinary Medicine, University of Gajah Mada , Yogyakarta , Indonesia.
authors.forename: Yuli P
authors.initials: YP
authors.lastname: Kristianingrum
authors.affiliation: Division of Pathology, Department of Clinic, Reproduction and Pathology, Faculty of Veterinary Medicine, Bogor Agricultural University , Bogor , Indonesia.
authors.forename: Ekowati
authors.initials: E
authors.lastname: Handaryani
authors.affiliation: Department of Experimental Medicine, Faculty of Health Science, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Jann
authors.initials: J
authors.lastname: Hau
keywords: cerebral amyloid angiopathy; degenerative disease; immunohistochemistry; neurofibrillary tangles; senile plaques