Asymmetric amyloid deposition in preclinical Alzheimer’s disease: A PET study

INTRODUCTION: The typical spatial pattern of amyloid-β (Aβ) in diagnosed Alzheimer’s disease (AD) is that of a symmetrical hemispheric distribution. However, Aβ may be asymmetrically distributed in early stages of AD. Aβ distribution on PET has previously been explored in MCI and AD, but it has yet to be directly investigated in preclinical AD (pAD). We examined how Aβ was distributed in individuals with pAD and MCI using (11)C-Pittsburgh Compound B (PiB) PET. METHODS: In this PET study, 79 subjects were retrospectively enrolled, including 34 controls, 24 pAD, and 21 MCI. All subjects underwent APOE genotyping, (11)C-PiB PET, MRI, and cognitive testing. We explored differences in Aβ load, Aβ lateralisation, and Aβ distribution, as well as associations between Aβ distribution and cognition. RESULTS: The Aβ asymmetry index (AI) differed between groups, with pAD having the highest Aβ AI as compared to both controls and MCI. There was no clear Aβ lateralisation in pAD, but there was a non-significant trend towards Aβ being more left-lateralised in MCI. There were no correlations between the cognitive scores and Aβ AI or Aβ lateralisation in pAD or MCI. CONCLUSION: The distribution of Aβ is most asymmetrical in pAD, as Aβ first starts accumulating, and it then becomes less asymmetrical in MCI, when Aβ has spread further, suggesting that more pronounced asymmetrical Aβ distribution may be a distinguishing factor in pAD. Longitudinal studies examining the distribution of Aβ across the AD continuum are needed.