title: Tau pathology in aged cynomolgus monkeys is progressive supranuclear palsy/corticobasal degeneration- but not Alzheimer disease-like -Ultrastructural mapping of tau by EDX.
abstract: Concomitant deposition of amyloid -beta protein (Aβ) and neuronal tau as neurofibrillary tangles in the human brain is a hallmark of Alzheimer disease (AD). Because these deposits increase during normal aging, it has been proposed that aging brains may also undergo AD-like changes. To investigate the neuropathological changes that occur in the aging primate brain, we examined 21 brains of cynomolgus monkeys (7-36 years old) for Aβ- and tau-positive lesions. We found, 1) extensive deposition of Aβ in brains of cynomolgus monkeys over 25 years of age, 2) selective deposition of 4-repeat tau as pretangles in neurons, and as coiled body-like structures in oligodendroglia-like cells and astrocytes, 3) preferential distribution of tau in the basal ganglia and neocortex rather than the hippocampus, and 4) age-associated increases in 30-34 kDa AT8- and RD4-positive tau fragments in sarkosyl-insoluble fractions. We further labeled tau-positive structures using diaminobezidine enhanced with nickel, and visualized nickel-labeled structures by energy-dispersive X-ray (EDX) analysis of ultrathin sections. This allowed us to distinguish between nickel-labeled tau and background electron-dense structures, and we found that tau localized to 20-25 nm straight filaments in oligodendroglia-like cells and neurons. Our results indicate that the cytopathology and distribution of tau deposits in aged cynomolgus brains resemble those of progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) rather than AD. Thus, even in the presence of Aβ, age-associated deposition of tau in non-human primates likely does not occur through AD-associated mechanisms.
authors.affiliation: Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo, 156-8506, Japan. uchihara-ts@igakuken.or.jp.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchihara
authors.affiliation: Histology Center, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo, 156-8506, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Endo
authors.affiliation: Histology Center, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo, 156-8506, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kondo
authors.affiliation: The Corporation for Production and Research of Laboratory Primates, Sakura 1-16-2, Tsukuba, Ibaraki, 305-0003, Japan.
authors.forename: Sachi
authors.initials: S
authors.lastname: Okabayashi
authors.affiliation: Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Hachimandai 1-1, Tsukuba, Ibaraki, 305-0843, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Shimozawa
authors.affiliation: Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Hachimandai 1-1, Tsukuba, Ibaraki, 305-0843, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yasutomi
authors.affiliation: Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya, Tokyo, 156-8506, Japan.
authors.forename: Eijiro
authors.initials: E
authors.lastname: Adachi
authors.affiliation: Section of Cell Biology and Pathology, Department of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology (NCGG), Moriika 7-430, Obu, Aichi, 474-8511, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kimura
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure*; D005260:Female; D007150:Immunohistochemistry; D008252:Macaca fascicularis / Q000378:metabolism*; D008297:Male; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D009836:Oligodendroglia / Q000378:metabolism / Q000648:ultrastructure; D013052:Spectrometry, X-Ray Emission; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: Aged monkey; Energy-dispersive X-ray analysis; Four-repeat tau; Immuno electron microscopy; Progressive supranuclear palsy