Hemispheric Asymmetry of Tau Pathology is Related to Asymmetric Amyloid Deposition in Alzheimer's Disease

Anijarv, T. E.; Ossenkoppele, R.; Smith, R.; Pichet Binette, A.; Collij, L. E.; Behjat, H. H.; Rittmo, J.; Karlsson, L.; Ahmadi, K.; Strandberg, O.; the Alzheimer's Disease Neuroimaging Initiative,; van Westen, D.; Vogel, J. W.; Stomrud, E.; Palmqvist, S.; Mattsson-Carlgren, N.; Spotorno, N.; Hansson, O.

doi:10.1101/2025.04.15.648728

bioRxiv · 10.1101/2025.04.15.648728

Hemispheric Asymmetry of Tau Pathology is Related to Asymmetric Amyloid Deposition in Alzheimer's Disease

Anijarv, T. E.·Ossenkoppele, R.·Smith, R.·Pichet Binette, A.·Collij, L. E.·Behjat, H. H.·Rittmo, J.·Karlsson, L.·Ahmadi, K.·Strandberg, O.·the Alzheimer's Disease Neuroimaging Initiative,·van Westen, D.·Vogel, J. W.·Stomrud, E.·Palmqvist, S.·Mattsson-Carlgren, N.·Spotorno, N.·Hansson, O.

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Abstract

The distribution of tau pathology in Alzheimers disease (AD) shows remarkable inter-individual heterogeneity, including hemispheric asymmetry. However, the factors driving this asymmetry remain poorly understood. We explored whether tau asymmetry is linked to i) reduced inter-hemispheric brain connectivity (potentially restricting tau spread), or ii) asymmetry in amyloid-beta (A{beta}) distribution (indicating greater hemisphere-specific vulnerability to AD pathology). 452 participants from the Swedish BioFINDER-2 cohort with evidence of both A{beta} pathology (CSF A{beta}42/40 or neocortical A{beta}-PET) and tau pathology (temporal tau-PET), were categorised as left asymmetric (n=102), symmetric (n=306), or right asymmetric (n=44) based on temporal lobe tau-PET uptake distribution. Edge-wise inter-hemispheric functional (RSfMRI; n=318) and structural connectivity (dMRI; n=352) patterns were examined but no differences in inter-hemispheric functional or structural connectivity were found between groups. However, a strong association was observed between tau and A{beta} laterality patterns based on PET uptake (n=233; {beta}=0.632, p<0.001), which was replicated in three independent cohorts (n=234; {beta}=0.535, p<0.001). In a longitudinal A{beta}-positive sample, baseline A{beta} asymmetry predicted the progression of tau laterality over time (n=289; {beta}=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 A{beta} pathology, underscoring the role of regional vulnerability in determining the distribution of AD pathology.

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Anijarv, T. E., Ossenkoppele, R., Smith, R., Pichet Binette, A., Collij, L. E., Behjat, H. H., Rittmo, J., Karlsson, L., Ahmadi, K., Strandberg, O., the Alzheimer's Disease Neuroimaging Initiative,, van Westen, D., Vogel, J. W., Stomrud, E., Palmqvist, S., Mattsson-Carlgren, N., Spotorno, N., Hansson, O.. 2025-04-19. Hemispheric Asymmetry of Tau Pathology is Related to Asymmetric Amyloid Deposition in Alzheimer's Disease. https://doi.org/10.1101/2025.04.15.648728

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