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Hippocampal Synaptic Alterations Associated with Tau Pathology in Primary Age-Related Tauopathy

Primary Age-Related Tauopathy (PART) is characterized by the aggregation of tau in the mesial temporal lobe in older individuals. High pathologic tau stage (Braak stage) or a high burden of hippocampal tau pathology have been associated with cognitive impairment in PART. However, the underlying mech...

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Autores principales: Morris, Meaghan, Coste, Gabrielle I, Redding-Ochoa, Javier, Guo, Haidan, Graves, Austin R, Troncoso, Juan C, Huganir, Richard L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980270/
https://www.ncbi.nlm.nih.gov/pubmed/36865237
http://dx.doi.org/10.1101/2023.02.22.23286323
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author Morris, Meaghan
Coste, Gabrielle I
Redding-Ochoa, Javier
Guo, Haidan
Graves, Austin R
Troncoso, Juan C
Huganir, Richard L
author_facet Morris, Meaghan
Coste, Gabrielle I
Redding-Ochoa, Javier
Guo, Haidan
Graves, Austin R
Troncoso, Juan C
Huganir, Richard L
author_sort Morris, Meaghan
collection PubMed
description Primary Age-Related Tauopathy (PART) is characterized by the aggregation of tau in the mesial temporal lobe in older individuals. High pathologic tau stage (Braak stage) or a high burden of hippocampal tau pathology have been associated with cognitive impairment in PART. However, the underlying mechanisms of cognitive impairment in PART are not well understood. Cognitive impairment in many neurodegenerative diseases correlates with synaptic loss, raising the question of whether synaptic loss occurs in PART. To address this, we investigated synaptic changes associated with tau Braak stage and a high tau pathology burden in PART using synaptophysin and phospho-tau immunofluorescence. We compared twelve cases of definite PART with six young controls and six Alzheimer’s disease cases. In this study, we identified loss of synaptophysin puncta and intensity in the CA2 region of the hippocampus in cases of PART with either a high stage (Braak IV) or a high burden of neuritic tau pathology. There was also loss of synaptophysin intensity in CA3 associated with a high stage or high burden of tau pathology. Loss of synaptophysin signal was present in AD, but the pattern was distinct from that seen in PART. These novel findings suggest the presence of synaptic loss in PART associated with either a high hippocampal tau burden or a Braak stage IV. These synaptic changes raise the possibility that synaptic loss in PART could contribute to cognitive impairment, though future studies including cognitive assessments are needed to address this question.
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spelling pubmed-99802702023-03-03 Hippocampal Synaptic Alterations Associated with Tau Pathology in Primary Age-Related Tauopathy Morris, Meaghan Coste, Gabrielle I Redding-Ochoa, Javier Guo, Haidan Graves, Austin R Troncoso, Juan C Huganir, Richard L medRxiv Article Primary Age-Related Tauopathy (PART) is characterized by the aggregation of tau in the mesial temporal lobe in older individuals. High pathologic tau stage (Braak stage) or a high burden of hippocampal tau pathology have been associated with cognitive impairment in PART. However, the underlying mechanisms of cognitive impairment in PART are not well understood. Cognitive impairment in many neurodegenerative diseases correlates with synaptic loss, raising the question of whether synaptic loss occurs in PART. To address this, we investigated synaptic changes associated with tau Braak stage and a high tau pathology burden in PART using synaptophysin and phospho-tau immunofluorescence. We compared twelve cases of definite PART with six young controls and six Alzheimer’s disease cases. In this study, we identified loss of synaptophysin puncta and intensity in the CA2 region of the hippocampus in cases of PART with either a high stage (Braak IV) or a high burden of neuritic tau pathology. There was also loss of synaptophysin intensity in CA3 associated with a high stage or high burden of tau pathology. Loss of synaptophysin signal was present in AD, but the pattern was distinct from that seen in PART. These novel findings suggest the presence of synaptic loss in PART associated with either a high hippocampal tau burden or a Braak stage IV. These synaptic changes raise the possibility that synaptic loss in PART could contribute to cognitive impairment, though future studies including cognitive assessments are needed to address this question. Cold Spring Harbor Laboratory 2023-06-07 /pmc/articles/PMC9980270/ /pubmed/36865237 http://dx.doi.org/10.1101/2023.02.22.23286323 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Morris, Meaghan
Coste, Gabrielle I
Redding-Ochoa, Javier
Guo, Haidan
Graves, Austin R
Troncoso, Juan C
Huganir, Richard L
Hippocampal Synaptic Alterations Associated with Tau Pathology in Primary Age-Related Tauopathy
title Hippocampal Synaptic Alterations Associated with Tau Pathology in Primary Age-Related Tauopathy
title_full Hippocampal Synaptic Alterations Associated with Tau Pathology in Primary Age-Related Tauopathy
title_fullStr Hippocampal Synaptic Alterations Associated with Tau Pathology in Primary Age-Related Tauopathy
title_full_unstemmed Hippocampal Synaptic Alterations Associated with Tau Pathology in Primary Age-Related Tauopathy
title_short Hippocampal Synaptic Alterations Associated with Tau Pathology in Primary Age-Related Tauopathy
title_sort hippocampal synaptic alterations associated with tau pathology in primary age-related tauopathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980270/
https://www.ncbi.nlm.nih.gov/pubmed/36865237
http://dx.doi.org/10.1101/2023.02.22.23286323
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