Hemispheric asymmetry of tau pathology is related to asymmetric amyloid deposition in Alzheimer’s Disease
- Toomas Erik Anijärv
- Rik Ossenkoppele
- Ruben Smith
- Alexa Pichet-Binette
- Lyduine E. Collij
- Harry H. Behjat
- Jonathan Rittmo
- Linda Karlsson
- Khazar Ahmadi
- Olof Strandberg
- Michael Weiner
- Paul Aisen
- Ronald Petersen
- Clifford R. Jack
- William Jagust
- Susan Landau
- Monica Rivera-Mindt
- Ozioma Okonkwo
- Leslie M. Shaw
- Edward B. Lee
- Arthur W. Toga
- Laurel Beckett
- Danielle Harvey
- Robert C. Green
- Andrew J. Saykin
- Kwangsik Nho
- Richard J. Perrin
- Duygu Tosun
- Danielle van Westen
- Jacob W. Vogel
- Erik Stomrud
- Sebastian Palmqvist
- Niklas Mattsson-Carlgren
- Nicola Spotorno
- Oskar Hansson
2025-09-05
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.