Combinatorial model of amyloid β and tau reveals synergy between amyloid deposits and tangle formation.

Autor: Koller EJ; Department of Neuroscience, University of Florida, Gainesville, Florida, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA.; Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA., Ibanez KR; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA., Vo Q; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA., McFarland KN; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA.; Department of Neurology, University of Florida, Gainesville, Florida, USA., Gonzalez De La Cruz E; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA., Zobel L; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA., Williams T; Department of Neuroscience, University of Florida, Gainesville, Florida, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA., Xu G; Department of Neuroscience, University of Florida, Gainesville, Florida, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA., Ryu D; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA., Patel P; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA., Giasson BI; Department of Neuroscience, University of Florida, Gainesville, Florida, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA.; McKnight Brain Institute, University of Florida, Gainesville, Florida, USA., Prokop S; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA.; McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.; Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, USA., Chakrabarty P; Department of Neuroscience, University of Florida, Gainesville, Florida, USA.; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, Florida, USA.; McKnight Brain Institute, University of Florida, Gainesville, Florida, USA.
Jazyk: angličtina
Zdroj: Neuropathology and applied neurobiology [Neuropathol Appl Neurobiol] 2022 Feb; Vol. 48 (2), pp. e12779. Date of Electronic Publication: 2021 Dec 10.
DOI: 10.1111/nan.12779
Abstrakt: Aims: To illuminate the pathological synergy between Aβ and tau leading to emergence of neurofibrillary tangles (NFT) in Alzheimer's disease (AD), here, we have performed a comparative neuropathological study utilising three distinctive variants of human tau (WT tau, P301L mutant tau and S320F mutant tau). Previously, in non-transgenic mice, we showed that WT tau or P301L tau does not form NFT while S320F tau can spontaneously aggregate into NFT, allowing us to test the selective vulnerability of these different tau conformations to the presence of Aβ plaques.
Methods: We injected recombinant AAV-tau constructs into neonatal APP transgenic TgCRND8 mice or into 3-month-old TgCRND8 mice; both cohorts were aged 3 months post injection. This allowed us to test how different tau variants synergise with soluble forms of Aβ (pre-deposit cohort) or with frank Aβ deposits (post-deposit cohort).
Results: Expression of WT tau did not produce NFT or altered Aβ in either cohort. In the pre-deposit cohort, S320F tau induced Aβ plaque deposition, neuroinflammation and synaptic abnormalities, suggesting that early tau tangles affect the amyloid cascade. In the post-deposit cohort, contemporaneous expression of S320F tau did not exacerbate amyloid pathology, showing a dichotomy in Aβ-tau synergy based on the nature of Aβ. P301L tau produced NFT-type inclusions in the post-deposit cohort, but not in the pre-deposit cohort, indicating pathological synergy with pre-existing Aβ deposits.
Conclusions: Our data show that different tau mutations representing specific folding variants of tau synergise with Aβ to different extents, depending on the presence of cerebral deposits.
(© 2021 British Neuropathological Society.)
Databáze: MEDLINE
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