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Nicolai Franzmeier

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About Nicolai Franzmeier:

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SEEK ID: http://localhost:3000/people/40

Location: Germany

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Organisms: Mus musculus, Rattus norvegicus, Homo sapiens, Macaca mulatta, Sus scrofa, Danio rerio

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Klinikum der Universität München

Country: Germany

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Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer's disease.

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Nicolai Franzmeier

Matthias Brendel

Abstract (Expand)

For 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.

Authors: Alexa Pichet Binette, Nicolai Franzmeier, Nicola Spotorno, Michael Ewers, Matthias Brendel, Davina Biel, Olof Strandberg, Shorena Janelidze, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Ruben Smith, Erik Stomrud, Rik Ossenkoppele, Oskar Hansson

Date Published: 4th Nov 2022

Publication Type: Journal

PubMed ID: 36333294

DOI: 10.1038/s41467-022-34129-4

Citation: Nature communications,13(1):6635

Created: 25th Oct 2024 at 10:06

(v.1.15.0)

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