Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia
Abstract Objective To investigate the relationship between the topography of amyloid‐β plaques, tau neurofibrillary tangles, and the overlap between the two, with cognitive dysfunction in individuals without dementia. Methods We evaluated 154 individuals who were assessed with amyloid‐β PET with [18...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2021-10-01
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| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.51457 |
| _version_ | 1818727048758165504 |
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| author | Joseph Therriault Tharick A. Pascoal Marcus Sefranek Sulantha Mathotaarachchi Andrea L. Benedet Mira Chamoun Firoza Z. Lussier Cécile Tissot Bruna Bellaver Pamela Lukasewicz Ferreira Eduardo R. Zimmer Paramita Saha‐Chaudhuri Serge Gauthier Pedro Rosa‐Neto the Alzheimer's Disease Neuroimaging Initiative |
| author_facet | Joseph Therriault Tharick A. Pascoal Marcus Sefranek Sulantha Mathotaarachchi Andrea L. Benedet Mira Chamoun Firoza Z. Lussier Cécile Tissot Bruna Bellaver Pamela Lukasewicz Ferreira Eduardo R. Zimmer Paramita Saha‐Chaudhuri Serge Gauthier Pedro Rosa‐Neto the Alzheimer's Disease Neuroimaging Initiative |
| author_sort | Joseph Therriault |
| collection | DOAJ |
| description | Abstract Objective To investigate the relationship between the topography of amyloid‐β plaques, tau neurofibrillary tangles, and the overlap between the two, with cognitive dysfunction in individuals without dementia. Methods We evaluated 154 individuals who were assessed with amyloid‐β PET with [18F]AZD4694, tau‐PET with [18F]MK6240, structural MRI, and neuropsychological testing. We also evaluated an independent cohort of 240 individuals who were assessed with amyloid‐β PET with [18F]Florbetapir, tau‐PET with [18F]Flortaucipir, structural MRI, and neuropsychological testing. Using the VoxelStats toolbox, we conducted voxel‐wise linear regressions between amyloid‐PET, tau‐PET, and their interaction with cognitive function, correcting for age, sex, and years of education. Results In both cohorts, we observed that tau‐PET standardized uptake value ratio in medial temporal lobes was associated with clinical dementia rating Sum of Boxes (CDR‐SoB) scores independently of local amyloid‐PET uptake (FWE corrected at p < 0.001). We also observed in both cohorts that in regions of the neocortex, associations between neocortical tau‐PET and clinical function were dependent on local amyloid‐PET (FWE corrected at p < 0.001). Interpretation In medial temporal brain regions, characterized by the accumulation of tau pathology in the absence of amyloid‐β, tau had direct associations with cognitive dysfunction. In brain regions characterized by the accumulation of both amyloid‐β and tau pathologies such as the posterior cingulate and medial frontal cortices, tau’s relationship with cognitive dysfunction was dependent on local amyloid‐β concentrations. Our results provide evidence that amyloid‐β in Alzheimer’s disease influences cognition by potentiating the deleterious effects of tau pathology. |
| first_indexed | 2024-12-17T22:07:54Z |
| format | Article |
| id | doaj.art-883ae9db72494384b227a029fb4a04f1 |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-12-17T22:07:54Z |
| publishDate | 2021-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-883ae9db72494384b227a029fb4a04f12022-12-21T21:30:48ZengWileyAnnals of Clinical and Translational Neurology2328-95032021-10-018102083209210.1002/acn3.51457Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementiaJoseph Therriault0Tharick A. Pascoal1Marcus Sefranek2Sulantha Mathotaarachchi3Andrea L. Benedet4Mira Chamoun5Firoza Z. Lussier6Cécile Tissot7Bruna Bellaver8Pamela Lukasewicz Ferreira9Eduardo R. Zimmer10Paramita Saha‐Chaudhuri11Serge Gauthier12Pedro Rosa‐Neto13the Alzheimer's Disease Neuroimaging InitiativeTranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaTranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaTranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaTranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaTranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaTranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaTranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaTranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaGraduate Program in Biological Sciences: Biochemistry Universidade Federal do Rio Grande do Sul Porto Alegre BrazilGraduate Program in Biological Sciences: Biochemistry Universidade Federal do Rio Grande do Sul Porto Alegre BrazilGraduate Program in Biological Sciences: Biochemistry Universidade Federal do Rio Grande do Sul Porto Alegre BrazilDepartment of Mathematics and Statistics University of Vermont VermontUSATranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaTranslational Neuroimaging Laboratory The McGill University Research Centre for Studies in Aging Montreal CanadaAbstract Objective To investigate the relationship between the topography of amyloid‐β plaques, tau neurofibrillary tangles, and the overlap between the two, with cognitive dysfunction in individuals without dementia. Methods We evaluated 154 individuals who were assessed with amyloid‐β PET with [18F]AZD4694, tau‐PET with [18F]MK6240, structural MRI, and neuropsychological testing. We also evaluated an independent cohort of 240 individuals who were assessed with amyloid‐β PET with [18F]Florbetapir, tau‐PET with [18F]Flortaucipir, structural MRI, and neuropsychological testing. Using the VoxelStats toolbox, we conducted voxel‐wise linear regressions between amyloid‐PET, tau‐PET, and their interaction with cognitive function, correcting for age, sex, and years of education. Results In both cohorts, we observed that tau‐PET standardized uptake value ratio in medial temporal lobes was associated with clinical dementia rating Sum of Boxes (CDR‐SoB) scores independently of local amyloid‐PET uptake (FWE corrected at p < 0.001). We also observed in both cohorts that in regions of the neocortex, associations between neocortical tau‐PET and clinical function were dependent on local amyloid‐PET (FWE corrected at p < 0.001). Interpretation In medial temporal brain regions, characterized by the accumulation of tau pathology in the absence of amyloid‐β, tau had direct associations with cognitive dysfunction. In brain regions characterized by the accumulation of both amyloid‐β and tau pathologies such as the posterior cingulate and medial frontal cortices, tau’s relationship with cognitive dysfunction was dependent on local amyloid‐β concentrations. Our results provide evidence that amyloid‐β in Alzheimer’s disease influences cognition by potentiating the deleterious effects of tau pathology.https://doi.org/10.1002/acn3.51457 |
| spellingShingle | Joseph Therriault Tharick A. Pascoal Marcus Sefranek Sulantha Mathotaarachchi Andrea L. Benedet Mira Chamoun Firoza Z. Lussier Cécile Tissot Bruna Bellaver Pamela Lukasewicz Ferreira Eduardo R. Zimmer Paramita Saha‐Chaudhuri Serge Gauthier Pedro Rosa‐Neto the Alzheimer's Disease Neuroimaging Initiative Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia Annals of Clinical and Translational Neurology |
| title | Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia |
| title_full | Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia |
| title_fullStr | Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia |
| title_full_unstemmed | Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia |
| title_short | Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia |
| title_sort | amyloid dependent and amyloid independent effects of tau in individuals without dementia |
| url | https://doi.org/10.1002/acn3.51457 |
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