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Hemispheric asymmetry of tau pathology is related to asymmetric amyloid deposition in Alzheimer's Disease

Anijärv, Toomas Erik LU orcid ; Ossenkoppele, Rik LU ; Smith, Ruben LU ; Pichet Binette, Alexa LU ; Collij, Lyduine E. LU ; Behjat, Harry H. LU ; Rittmo, Jonathan LU orcid ; Karlsson, Linda LU orcid ; Ahmadi, Khazar LU and Strandberg, Olof LU , et al. (2025) In Nature Communications 16(1).
Abstract

The distribution of tau pathology in Alzheimer's disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. Here we explore whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or ii) asymmetry in amyloid-beta (Aβ) distribution (indicating greater hemisphere-specific vulnerability to AD pathology). We include 452 participants from the Swedish BioFINDER-2 cohort with evidence of both Aβ pathology (CSF Aβ42/40 or neocortical Aβ-PET) and tau pathology (temporal tau-PET), categorising them as left asymmetric (n = 102), symmetric (n = 306), or right asymmetric (n = 44)... (More)

The distribution of tau pathology in Alzheimer's disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. Here we explore whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or ii) asymmetry in amyloid-beta (Aβ) distribution (indicating greater hemisphere-specific vulnerability to AD pathology). We include 452 participants from the Swedish BioFINDER-2 cohort with evidence of both Aβ pathology (CSF Aβ42/40 or neocortical Aβ-PET) and tau pathology (temporal tau-PET), categorising them as left asymmetric (n = 102), symmetric (n = 306), or right asymmetric (n = 44) based on temporal lobe tau-PET uptake distribution. We assess edge-wise inter-hemispheric functional (RSfMRI; n = 318) and structural connectivity (dMRI; n = 352) but find no association between tau asymmetry and connectivity. In contrast, we observe a strong association between tau and Aβ laterality patterns based on PET uptake (n = 233; β = 0.632, p < 0.001), which we replicate in three independent cohorts (n = 234; β = 0.535, p < 0.001). In a longitudinal Aβ-positive sample, we show that baseline Aβ asymmetry predicts progression of tau laterality over time (n = 289; β = 0.025, p = 0.028). These findings suggest that tau asymmetry is not associated with a weaker inter-hemispheric connectivity but might reflect hemispheric differences in vulnerability to Aβ pathology, underscoring the role of regional vulnerability in determining the distribution of AD pathology.

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type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
16
issue
1
article number
8232
publisher
Nature Publishing Group
external identifiers
  • pmid:40913038
  • scopus:105015489558
ISSN
2041-1723
DOI
10.1038/s41467-025-63564-2
language
English
LU publication?
yes
id
1b419c04-7030-406e-a1b6-1d038d0a31bd
date added to LUP
2025-10-15 13:00:01
date last changed
2025-10-16 11:01:10
@article{1b419c04-7030-406e-a1b6-1d038d0a31bd,
  abstract     = {{<p>The distribution of tau pathology in Alzheimer's disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. Here we explore whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or ii) asymmetry in amyloid-beta (Aβ) distribution (indicating greater hemisphere-specific vulnerability to AD pathology). We include 452 participants from the Swedish BioFINDER-2 cohort with evidence of both Aβ pathology (CSF Aβ42/40 or neocortical Aβ-PET) and tau pathology (temporal tau-PET), categorising them as left asymmetric (n = 102), symmetric (n = 306), or right asymmetric (n = 44) based on temporal lobe tau-PET uptake distribution. We assess edge-wise inter-hemispheric functional (RSfMRI; n = 318) and structural connectivity (dMRI; n = 352) but find no association between tau asymmetry and connectivity. In contrast, we observe a strong association between tau and Aβ laterality patterns based on PET uptake (n = 233; β = 0.632, p &lt; 0.001), which we replicate in three independent cohorts (n = 234; β = 0.535, p &lt; 0.001). In a longitudinal Aβ-positive sample, we show that baseline Aβ asymmetry predicts progression of tau laterality over time (n = 289; β = 0.025, p = 0.028). These findings suggest that tau asymmetry is not associated with a weaker inter-hemispheric connectivity but might reflect hemispheric differences in vulnerability to Aβ pathology, underscoring the role of regional vulnerability in determining the distribution of AD pathology.</p>}},
  author       = {{Anijärv, Toomas Erik and Ossenkoppele, Rik and Smith, Ruben and Pichet Binette, Alexa and Collij, Lyduine E. and Behjat, Harry H. and Rittmo, Jonathan and Karlsson, Linda and Ahmadi, Khazar and Strandberg, Olof and van Westen, Danielle and Vogel, Jacob W. and Stomrud, Erik and Palmqvist, Sebastian and Mattsson-Carlgren, Niklas and Spotorno, Nicola and Hansson, Oskar}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Hemispheric asymmetry of tau pathology is related to asymmetric amyloid deposition in Alzheimer's Disease}},
  url          = {{http://dx.doi.org/10.1038/s41467-025-63564-2}},
  doi          = {{10.1038/s41467-025-63564-2}},
  volume       = {{16}},
  year         = {{2025}},
}