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

Anijärv TE, Ossenkoppele R, Smith R, Pichet Binette A, Collij LE, Behjat HH, Rittmo J, Karlsson L, Ahmadi K, Strandberg O, Alzheimer’s Disease Neuroimaging Initiative , van Westen D, Vogel JW, Stomrud E, Palmqvist S, Mattsson-Carlgren N, Spotorno N, Hansson O

Nat Commun 16 (1) 8232 [2025-09-05; online 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.

PubMed 40913038

DOI 10.1038/s41467-025-63564-2

Crossref 10.1038/s41467-025-63564-2

pmc: PMC12413461
pii: 10.1038/s41467-025-63564-2