> Detailanzeige
Pichet Binette, Alexa;
Franzmeier, Nicolai;
Spotorno, Nicola;
Ewers, Michael;
Brendel, Matthias;
Biel, Davina;
Weiner, Michael;
Aisen, Paul;
Petersen, Ronald;
Jack, Clifford R.;
Jagust, William;
Trojanowki, John Q.;
Toga, Arthur W.;
Beckett, Laurel;
Green, Robert C.;
Saykin, Andrew J.;
Morris, John;
Shaw, Leslie M.;
Liu, Enchi;
Montine, Tom;
Thomas, Ronald G.;
Donohue, Michael;
Walter, Sarah;
Gessert, Devon;
[...]
Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer’s disease
Teilen
Literatur-
verwaltung
Direktlink
Zur
Merkliste
Lösche von
Merkliste
Per Email teilen
Auf Twitter teilen
Auf Facebook teilen
Per Whatsapp teilen
- Medientyp: E-Artikel
- Titel: Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer’s disease
- Beteiligte: Pichet Binette, Alexa; Franzmeier, Nicolai; Spotorno, Nicola; Ewers, Michael; Brendel, Matthias; Biel, Davina; Weiner, Michael; Aisen, Paul; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John Q.; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Saykin, Andrew J.; Morris, John; Shaw, Leslie M.; Liu, Enchi; Montine, Tom; Thomas, Ronald G.; Donohue, Michael; Walter, Sarah; Gessert, Devon; [...]
-
Erschienen:
Springer Science and Business Media LLC, 2022
- Erschienen in: Nature Communications, 13 (2022) 1
- Sprache: Englisch
- DOI: 10.1038/s41467-022-34129-4
- ISSN: 2041-1723
- Entstehung:
- Anmerkungen:
- Beschreibung: AbstractFor optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, we need to better understand the pathophysiological cascade of Aβ- and tau-related processes. Therefore, we set out to investigate how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with PET and subsequent cognitive decline across the Alzheimer’s disease (AD) continuum. Using human cross-sectional and longitudinal neuroimaging and cognitive assessment data, we show that in early stages of AD, increased concentration of soluble CSF p-tau is strongly associated with accumulation of insoluble tau aggregates across the brain, and CSF p-tau levels mediate the effect of Aβ on tau aggregation. Further, higher soluble p-tau concentrations are mainly related to faster accumulation of tau aggregates in the regions with strong functional connectivity to individual tau epicenters. In this early stage, higher soluble p-tau concentrations is associated with cognitive decline, which is mediated by faster increase of tau aggregates. In contrast, in AD dementia, when Aβ fibrils and soluble p-tau levels have plateaued, cognitive decline is related to the accumulation rate of insoluble tau aggregates. Our data suggest that therapeutic approaches reducing soluble p-tau levels might be most favorable in early AD, before widespread insoluble tau aggregates.
- Zugangsstatus: Freier Zugang