Details

Autor(en) / Beteiligte

• Bellaver, Bruna
• Povala, Guilherme
• Ferreira, Pamela C. L.
• Ferrari-Souza, João Pedro
• Leffa, Douglas T.
• Lussier, Firoza Z.
• Benedet, Andréa L.
• Ashton, Nicholas J.
• Triana-Baltzer, Gallen
• Kolb, Hartmuth C.
• Tissot, Cécile
• Therriault, Joseph
• Servaes, Stijn
• Stevenson, Jenna
• Rahmouni, Nesrine
• Lopez, Oscar L.
• Tudorascu, Dana L.
• Villemagne, Victor L.
• Ikonomovic, Milos D.
• Gauthier, Serge
• Zimmer, Eduardo R.
• Zetterberg, Henrik
• Blennow, Kaj
• Aizenstein, Howard J.
• Klunk, William E.
• Snitz, Beth E.
• Maki, Pauline
• Thurston, Rebecca C.
• Cohen, Ann D.
• Ganguli, Mary
• Karikari, Thomas K.
• Rosa-Neto, Pedro
• Pascoal, Tharick A.

Titel

Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease

Ist Teil von

• Nature medicine, 2023-07, Vol.29 (7), p.1775-1781

Ort / Verlag

New York: Nature Publishing Group US

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.