Tau Aggregation Correlates with Amyloid Deposition in Both Mild Cognitive Impairment and Alzheimer’s Disease Subjects

Article type: Research Article

Authors: Dani, Melanie^a | Wood, Melanie^a | Mizoguchi, Ruth^a | Fan, Zhen^a | Edginton, Trudi^b | Hinz, Rainer^c | Win, Zarni^d | Brooks, David James^{a; e; f} | Edison, Paul^{a; *}

Affiliations: [a] Neurology Imaging Unit, Department of Medicine, Imperial College London, London, UK | [b] Department of Psychology, City University of London, London, UK | [c] Wolfson Molecular Imaging Centre, University of Manchester, Manchester, UK | [d] Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, UK | [e] Department of Nuclear Medicine, Aarhus University, Aarhus, Denmark | [f] Institute of Neuroscience, University of Newcastle upon Tyne, Newcastle University Campus for Ageing and Vitality, Newcastle, UK

Correspondence: [*] Correspondence to: Dr. Paul Edison MD, MRCP, PhD, FRCP, FRCPI, Neurology Imaging Unit, Division of Brain Sciences, Imperial College London, DuCane Road, Hammersmith Hospital, London, W12 0NN, UK. Tel.: +44 203 383 3725; Fax: +44 203 313 4320; E-mail: [email protected].

Abstract: Background:Amyloid plaque and tau-containing neurofibrillary tangles are important features of Alzheimer’s disease (AD). However, the relationship between these processes is still debated. Objective:We aimed to investigate local and distant relationships between tau and amyloid deposition in the cortex in mild cognitive impairment (MCI) and AD using PET imaging. Methods:Seventy-nine subjects (51 controls, 13 amyloid-positive MCI subjects, and 15 amyloid positive AD subjects) underwent MRI and 18F-flutemetamol PET. All MCI/AD subjects and 8 healthy controls as well as 33 healthy control subjects from the ADNI dataset also had 18F-AV1451 PET. Regional and distant correlations were examined after sampling target-to-cerebellar ratio images. Biological parametric mapping was used to evaluate voxel level correlations locally. Results:We found multiple clusters of voxels with highly significant positive correlations throughout the association cortex in both MCI and AD subjects. Conclusion:The multiple clusters of positive correlations indicate that tau and amyloid may interact locally and be involved in disease progression. Our findings suggest that targeting both pathologies may be required.

Keywords: Alzheimer’s disease, amyloid, mild cognitive impairment, PET, tau

DOI: 10.3233/JAD-181168

Journal: Journal of Alzheimer's Disease, vol. 70, no. 2, pp. 455-465, 2019