Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia

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...

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Veröffentlicht in:	Annals of clinical and translational neurology 2021-10, Vol.8 (10), p.2083-2092
Hauptverfasser:	Therriault, Joseph, Pascoal, Tharick A., Sefranek, Marcus, Mathotaarachchi, Sulantha, Benedet, Andrea L., Chamoun, Mira, Lussier, Firoza Z., Tissot, Cécile, Bellaver, Bruna, Lukasewicz, Pamela S., Zimmer, Eduardo R., Saha‐Chaudhuri, Paramita, Gauthier, Serge, Rosa‐Neto, Pedro
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Sprache:	eng
Schlagworte:	Aged Aged, 80 and over Algorithms Alzheimer's disease Amnesia - diagnostic imaging Amnesia - metabolism Amyloid beta-Peptides - metabolism Biomarkers Clinical Neurology Cognitive ability Cognitive Dysfunction - diagnostic imaging Cognitive Dysfunction - metabolism Cohort Studies Dementia Female Humans Hypotheses Life Sciences & Biomedicine Magnetic Resonance Imaging Male Medical imaging Middle Aged Neocortex - diagnostic imaging Neocortex - metabolism Neurosciences Neurosciences & Neurology Neurotoxicity Pathology Positron-Emission Tomography Science & Technology tau Proteins - metabolism
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creator	Therriault, Joseph Pascoal, Tharick A. Sefranek, Marcus Mathotaarachchi, Sulantha Benedet, Andrea L. Chamoun, Mira Lussier, Firoza Z. Tissot, Cécile Bellaver, Bruna Lukasewicz, Pamela S. Zimmer, Eduardo R. Saha‐Chaudhuri, Paramita Gauthier, Serge Rosa‐Neto, Pedro
description	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
doi_str_mv	10.1002/acn3.51457
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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. 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Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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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.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Algorithms</subject><subject>Alzheimer's disease</subject><subject>Amnesia - diagnostic imaging</subject><subject>Amnesia - metabolism</subject><subject>Amyloid beta-Peptides - metabolism</subject><subject>Biomarkers</subject><subject>Clinical Neurology</subject><subject>Cognitive ability</subject><subject>Cognitive Dysfunction - diagnostic imaging</subject><subject>Cognitive Dysfunction - metabolism</subject><subject>Cohort Studies</subject><subject>Dementia</subject><subject>Female</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Life Sciences & Biomedicine</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Middle Aged</subject><subject>Neocortex - diagnostic imaging</subject><subject>Neocortex - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Annals of clinical and translational neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Therriault, Joseph</au><au>Pascoal, Tharick A.</au><au>Sefranek, Marcus</au><au>Mathotaarachchi, Sulantha</au><au>Benedet, Andrea L.</au><au>Chamoun, Mira</au><au>Lussier, Firoza Z.</au><au>Tissot, Cécile</au><au>Bellaver, Bruna</au><au>Lukasewicz, Pamela S.</au><au>Zimmer, Eduardo R.</au><au>Saha‐Chaudhuri, Paramita</au><au>Gauthier, Serge</au><au>Rosa‐Neto, Pedro</au><aucorp>Alzheimers Dis Neuroimaging Initia</aucorp><aucorp>Alzheimer's Disease Neuroimaging Initiative</aucorp><aucorp>the Alzheimer's Disease Neuroimaging Initiative</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia</atitle><jtitle>Annals of clinical and translational neurology</jtitle><stitle>ANN CLIN TRANSL NEUR</stitle><addtitle>Ann Clin Transl Neurol</addtitle><date>2021-10</date><risdate>2021</risdate><volume>8</volume><issue>10</issue><spage>2083</spage><epage>2092</epage><pages>2083-2092</pages><issn>2328-9503</issn><eissn>2328-9503</eissn><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.</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>34617688</pmid><doi>10.1002/acn3.51457</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-7826-4781</orcidid><orcidid>https://orcid.org/0000-0003-2711-3833</orcidid><orcidid>https://orcid.org/0000-0001-9116-1376</orcidid><orcidid>https://orcid.org/0000-0001-9057-8014</orcidid><oa>free_for_read</oa></addata></record>
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subjects	Aged Aged, 80 and over Algorithms Alzheimer's disease Amnesia - diagnostic imaging Amnesia - metabolism Amyloid beta-Peptides - metabolism Biomarkers Clinical Neurology Cognitive ability Cognitive Dysfunction - diagnostic imaging Cognitive Dysfunction - metabolism Cohort Studies Dementia Female Humans Hypotheses Life Sciences & Biomedicine Magnetic Resonance Imaging Male Medical imaging Middle Aged Neocortex - diagnostic imaging Neocortex - metabolism Neurosciences Neurosciences & Neurology Neurotoxicity Pathology Positron-Emission Tomography Science & Technology tau Proteins - metabolism
title	Amyloid‐dependent and amyloid‐independent effects of Tau in individuals without dementia
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