Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer's disease
(2022) In Nature Communications 13(1). p.6635-6635- Abstract
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... (More)
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.
(Less)
- author
- author collaboration
- organization
-
- Clinical Memory Research (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- MR Physics (research group)
- Medical Radiation Physics, Lund
- Brain Injury After Cardiac Arrest (research group)
- WCMM-Wallenberg Centre for Molecular Medicine
- Neurology, Lund
- Regeneration in Movement Disorders (research group)
- publishing date
- 2022-11-04
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nature Communications
- volume
- 13
- issue
- 1
- pages
- 1 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85141890639
- pmid:36333294
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-022-34129-4
- language
- English
- LU publication?
- yes
- id
- 07bf1e35-fc85-4a61-be65-730d03b1afeb
- date added to LUP
- 2022-12-28 15:04:03
- date last changed
- 2024-09-21 09:07:08
@article{07bf1e35-fc85-4a61-be65-730d03b1afeb, abstract = {{<p>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.</p>}}, author = {{Pichet Binette, Alexa and Franzmeier, Nicolai and Spotorno, Nicola and Ewers, Michael and Brendel, Matthias and Biel, Davina and Strandberg, Olof and Janelidze, Shorena and Palmqvist, Sebastian and Mattsson-Carlgren, Niklas and Smith, Ruben and Stomrud, Erik and Ossenkoppele, Rik and Hansson, Oskar}}, issn = {{2041-1723}}, language = {{eng}}, month = {{11}}, number = {{1}}, pages = {{6635--6635}}, publisher = {{Nature Publishing Group}}, series = {{Nature Communications}}, title = {{Amyloid-associated increases in soluble tau relate to tau aggregation rates and cognitive decline in early Alzheimer's disease}}, url = {{http://dx.doi.org/10.1038/s41467-022-34129-4}}, doi = {{10.1038/s41467-022-34129-4}}, volume = {{13}}, year = {{2022}}, }