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Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease
by
Maki, Pauline
, Ferreira, Pamela C. L.
, Gauthier, Serge
, Bellaver, Bruna
, Snitz, Beth E.
, Tissot, Cécile
, Klunk, William E.
, Lopez, Oscar L.
, Triana-Baltzer, Gallen
, Thurston, Rebecca C.
, Servaes, Stijn
, Pascoal, Tharick A.
, Povala, Guilherme
, Ferrari-Souza, João Pedro
, Villemagne, Victor L.
, Therriault, Joseph
, Cohen, Ann D.
, Zimmer, Eduardo R.
, Aizenstein, Howard J.
, Ganguli, Mary
, Zetterberg, Henrik
, Stevenson, Jenna
, Benedet, Andréa L.
, Rosa-Neto, Pedro
, Leffa, Douglas T.
, Tudorascu, Dana L.
, Rahmouni, Nesrine
, Blennow, Kaj
, Karikari, Thomas K.
, Kolb, Hartmuth C.
, Lussier, Firoza Z.
, Ikonomovic, Milos D.
, Ashton, Nicholas J.
in
692/308/53/2423
/ 692/53/2422
/ 692/53/2423
/ 692/617/375/365/1283
/ Alzheimer's disease
/ Astrocytes
/ Biomarkers
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Clinical deterioration
/ Clinical trials
/ Emission analysis
/ Infectious Diseases
/ Metabolic Diseases
/ Molecular Biology
/ Molecular Medicine
/ Molekylärbiologi
/ Neurodegenerative diseases
/ Neurosciences
/ Pathology
/ Phosphorylation
/ Positron emission
/ Positron emission tomography
/ Tau protein
/ β-Amyloid
2023
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Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease
by
Maki, Pauline
, Ferreira, Pamela C. L.
, Gauthier, Serge
, Bellaver, Bruna
, Snitz, Beth E.
, Tissot, Cécile
, Klunk, William E.
, Lopez, Oscar L.
, Triana-Baltzer, Gallen
, Thurston, Rebecca C.
, Servaes, Stijn
, Pascoal, Tharick A.
, Povala, Guilherme
, Ferrari-Souza, João Pedro
, Villemagne, Victor L.
, Therriault, Joseph
, Cohen, Ann D.
, Zimmer, Eduardo R.
, Aizenstein, Howard J.
, Ganguli, Mary
, Zetterberg, Henrik
, Stevenson, Jenna
, Benedet, Andréa L.
, Rosa-Neto, Pedro
, Leffa, Douglas T.
, Tudorascu, Dana L.
, Rahmouni, Nesrine
, Blennow, Kaj
, Karikari, Thomas K.
, Kolb, Hartmuth C.
, Lussier, Firoza Z.
, Ikonomovic, Milos D.
, Ashton, Nicholas J.
in
692/308/53/2423
/ 692/53/2422
/ 692/53/2423
/ 692/617/375/365/1283
/ Alzheimer's disease
/ Astrocytes
/ Biomarkers
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Clinical deterioration
/ Clinical trials
/ Emission analysis
/ Infectious Diseases
/ Metabolic Diseases
/ Molecular Biology
/ Molecular Medicine
/ Molekylärbiologi
/ Neurodegenerative diseases
/ Neurosciences
/ Pathology
/ Phosphorylation
/ Positron emission
/ Positron emission tomography
/ Tau protein
/ β-Amyloid
2023
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Do you wish to request the book?
Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease
by
Maki, Pauline
, Ferreira, Pamela C. L.
, Gauthier, Serge
, Bellaver, Bruna
, Snitz, Beth E.
, Tissot, Cécile
, Klunk, William E.
, Lopez, Oscar L.
, Triana-Baltzer, Gallen
, Thurston, Rebecca C.
, Servaes, Stijn
, Pascoal, Tharick A.
, Povala, Guilherme
, Ferrari-Souza, João Pedro
, Villemagne, Victor L.
, Therriault, Joseph
, Cohen, Ann D.
, Zimmer, Eduardo R.
, Aizenstein, Howard J.
, Ganguli, Mary
, Zetterberg, Henrik
, Stevenson, Jenna
, Benedet, Andréa L.
, Rosa-Neto, Pedro
, Leffa, Douglas T.
, Tudorascu, Dana L.
, Rahmouni, Nesrine
, Blennow, Kaj
, Karikari, Thomas K.
, Kolb, Hartmuth C.
, Lussier, Firoza Z.
, Ikonomovic, Milos D.
, Ashton, Nicholas J.
in
692/308/53/2423
/ 692/53/2422
/ 692/53/2423
/ 692/617/375/365/1283
/ Alzheimer's disease
/ Astrocytes
/ Biomarkers
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer Research
/ Clinical deterioration
/ Clinical trials
/ Emission analysis
/ Infectious Diseases
/ Metabolic Diseases
/ Molecular Biology
/ Molecular Medicine
/ Molekylärbiologi
/ Neurodegenerative diseases
/ Neurosciences
/ Pathology
/ Phosphorylation
/ Positron emission
/ Positron emission tomography
/ Tau protein
/ β-Amyloid
2023
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Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease
Journal Article
Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease
2023
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Overview
An unresolved question for the understanding of Alzheimer’s disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effects in pathological tau phosphorylation. Here, in a biomarker study across three cohorts (
n
= 1,016), we tested whether astrocyte reactivity modulates the association of Aβ with tau phosphorylation in CU individuals. We found that Aβ was associated with increased plasma phosphorylated tau only in individuals positive for astrocyte reactivity (Ast
+
). Cross-sectional and longitudinal tau–positron emission tomography analyses revealed an AD-like pattern of tau tangle accumulation as a function of Aβ only in CU Ast
+
individuals. Our findings suggest astrocyte reactivity as an important upstream event linking Aβ with initial tau pathology, which may have implications for the biological definition of preclinical AD and for selecting CU individuals for clinical trials.
Cross-sectional and longitudinal analyses of tau pathology in preclinical Alzheimer’s disease reveal that tau tangles accumulate as a function of amyloid-β burden only in individuals positive for an astrocyte reactivity biomarker.
Publisher
Nature Publishing Group US,Nature Publishing Group
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