Distinct subcellular localization of tau and alpha-synuclein in lewy body disease
Abstract Lewy bodies and neurofibrillary tangles, composed of α-synuclein (α-syn) and tau, respectively, often are found together in the same brain and correlate with worsening cognition. Human postmortem studies show colocalization of α-syn and tau occurs in Lewy bodies, but with limited effort to...
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BMC
2025-01-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-024-01913-w |
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| author | D. Luke Fischer Marissa Menard Omar Z. Abdelaziz Nicholas M. Kanaan Virginia G. Cobbs Richard E. Kennedy Geidy E. Serrano Thomas G. Beach Laura A. Volpicelli-Daley |
| author_facet | D. Luke Fischer Marissa Menard Omar Z. Abdelaziz Nicholas M. Kanaan Virginia G. Cobbs Richard E. Kennedy Geidy E. Serrano Thomas G. Beach Laura A. Volpicelli-Daley |
| author_sort | D. Luke Fischer |
| collection | DOAJ |
| description | Abstract Lewy bodies and neurofibrillary tangles, composed of α-synuclein (α-syn) and tau, respectively, often are found together in the same brain and correlate with worsening cognition. Human postmortem studies show colocalization of α-syn and tau occurs in Lewy bodies, but with limited effort to quantify colocalization. In this study, postmortem middle temporal gyrus tissue from decedents (n = 9) without temporal lobe disease (control) or with Lewy body disease (LBD) was immunofluorescently labeled with antibodies to phosphorylated α-syn (p-α-syn), tau phosphorylated at Ser202/Thr205 (p-tau), or exposure of tau’s phosphatase-activating domain (PAD-tau) as a marker of early tau aggregates. Immunofluorescence for major-histocompatibility complex class 2 (MHCII) and ionized calcium binding adaptor molecule 1 (Iba1) also was performed because inflammation is an additional pathological hallmark of LBDs, and they were a positive control for two markers known to colocalize. The abundance of p-α-syn, p-tau, and MHCII was significantly associated with diagnosis of LBD. Quantification of colocalization showed that MHCII and Iba1 colocalized, demonstrating activated immune cells are mostly microglia. However, p-α-syn rarely colocalized with p-tau or PAD-tau, although the overlap of p-α-syn with PAD-tau was significantly associated with LBD. In the rare cases pathologic α-syn and pathologic tau were found in the same Lewy body or Lewy neurite, tau appeared to surround α-syn but did not colocalize within the same structure. The relationship between tau and α-syn copathology is important for explaining clinical symptoms, severity, and progression, but there is no evidence for frequent, direct protein-protein interactions in the middle temporal gyrus. |
| format | Article |
| id | doaj-art-ebf4ff12a1204f5bb452069b9ead6560 |
| institution | Kabale University |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-ebf4ff12a1204f5bb452069b9ead65602025-01-26T12:57:21ZengBMCActa Neuropathologica Communications2051-59602025-01-0113111310.1186/s40478-024-01913-wDistinct subcellular localization of tau and alpha-synuclein in lewy body diseaseD. Luke Fischer0Marissa Menard1Omar Z. Abdelaziz2Nicholas M. Kanaan3Virginia G. Cobbs4Richard E. Kennedy5Geidy E. Serrano6Thomas G. Beach7Laura A. Volpicelli-Daley8Center for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at BirminghamCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at BirminghamCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at BirminghamDepartment of Translational Neuroscience, College of Human Medicine, Michigan State UniversityCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at BirminghamDepartment of Medicine, University of Alabama at BirminghamBanner Sun Health Research InstituteBanner Sun Health Research InstituteCenter for Neurodegeneration and Experimental Therapeutics, Department of Neurology, University of Alabama at BirminghamAbstract Lewy bodies and neurofibrillary tangles, composed of α-synuclein (α-syn) and tau, respectively, often are found together in the same brain and correlate with worsening cognition. Human postmortem studies show colocalization of α-syn and tau occurs in Lewy bodies, but with limited effort to quantify colocalization. In this study, postmortem middle temporal gyrus tissue from decedents (n = 9) without temporal lobe disease (control) or with Lewy body disease (LBD) was immunofluorescently labeled with antibodies to phosphorylated α-syn (p-α-syn), tau phosphorylated at Ser202/Thr205 (p-tau), or exposure of tau’s phosphatase-activating domain (PAD-tau) as a marker of early tau aggregates. Immunofluorescence for major-histocompatibility complex class 2 (MHCII) and ionized calcium binding adaptor molecule 1 (Iba1) also was performed because inflammation is an additional pathological hallmark of LBDs, and they were a positive control for two markers known to colocalize. The abundance of p-α-syn, p-tau, and MHCII was significantly associated with diagnosis of LBD. Quantification of colocalization showed that MHCII and Iba1 colocalized, demonstrating activated immune cells are mostly microglia. However, p-α-syn rarely colocalized with p-tau or PAD-tau, although the overlap of p-α-syn with PAD-tau was significantly associated with LBD. In the rare cases pathologic α-syn and pathologic tau were found in the same Lewy body or Lewy neurite, tau appeared to surround α-syn but did not colocalize within the same structure. The relationship between tau and α-syn copathology is important for explaining clinical symptoms, severity, and progression, but there is no evidence for frequent, direct protein-protein interactions in the middle temporal gyrus.https://doi.org/10.1186/s40478-024-01913-wTauAlpha-synucleinLewy bodyNeurofibrillary tangleCopathology |
| spellingShingle | D. Luke Fischer Marissa Menard Omar Z. Abdelaziz Nicholas M. Kanaan Virginia G. Cobbs Richard E. Kennedy Geidy E. Serrano Thomas G. Beach Laura A. Volpicelli-Daley Distinct subcellular localization of tau and alpha-synuclein in lewy body disease Acta Neuropathologica Communications Tau Alpha-synuclein Lewy body Neurofibrillary tangle Copathology |
| title | Distinct subcellular localization of tau and alpha-synuclein in lewy body disease |
| title_full | Distinct subcellular localization of tau and alpha-synuclein in lewy body disease |
| title_fullStr | Distinct subcellular localization of tau and alpha-synuclein in lewy body disease |
| title_full_unstemmed | Distinct subcellular localization of tau and alpha-synuclein in lewy body disease |
| title_short | Distinct subcellular localization of tau and alpha-synuclein in lewy body disease |
| title_sort | distinct subcellular localization of tau and alpha synuclein in lewy body disease |
| topic | Tau Alpha-synuclein Lewy body Neurofibrillary tangle Copathology |
| url | https://doi.org/10.1186/s40478-024-01913-w |
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