title: Tau-targeted immunization impedes progression of neurofibrillary histopathology in aged P301L tau transgenic mice.
abstract: In Alzheimer's disease (AD) brains, the microtubule-associated protein tau and amyloid-β (Aβ) deposit as intracellular neurofibrillary tangles (NFTs) and extracellular plaques, respectively. Tau deposits are furthermore found in a significant number of frontotemporal dementia cases. These diseases are characterized by progressive neurodegeneration, the loss of intellectual capabilities and behavioral changes. Unfortunately, the currently available therapies are limited to symptomatic relief. While active immunization against Aβ has shown efficacy in both various AD mouse models and patients with AD, immunization against pathogenic tau has only recently been shown to prevent pathology in young tau transgenic mice. However, if translated to humans, diagnosis and treatment would be routinely done when symptoms are overt, meaning that the histopathological changes have already progressed. Therefore, we used active immunization to target pathogenic tau in 4, 8, and 18 months-old P301L tau transgenic pR5 mice that have an onset of NFT pathology at 6 months of age. In all age groups, NFT pathology was significantly reduced in treated compared to control pR5 mice. Similarly, phosphorylation of tau at pathological sites was reduced. In addition, increased astrocytosis was found in the oldest treated group. Taken together, our data suggests that tau-targeted immunization slows the progression of NFT pathology in mice, with practical implications for human patients.
authors.affiliation: Laboratory for Translational Neurodegeneration, Brain and Mind Research Institute, The University of Sydney, Camperdown, New South Wales, Australia.
authors.forename: Mian
authors.initials: M
authors.lastname: Bi
authors.forename: Arne
authors.initials: A
authors.lastname: Ittner
authors.forename: Yazi D
authors.initials: YD
authors.lastname: Ke
authors.forename: Jürgen
authors.initials: J
authors.lastname: Götz
authors.forename: Lars M
authors.initials: LM
authors.lastname: Ittner
mesh_terms: D000375:Aging / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D018450:Disease Progression; D005911:Gliosis / Q000150:complications / Q000473:pathology; D006801:Humans; D007109:Immunity / Q000276:immunology; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000473:pathology*; D010766:Phosphorylation; D014611:Vaccination; D016875:tau Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
chemical_list: D016875:tau Proteins