Cerebrospinal Fluid Biomarkers are Differentially Related to Structural and Functional Changes in Dementia of the Alzheimer’s Type

Article type: Research Article

Authors: Malpas, Charles B.^{a; b; c; *} | Saling, Michael M.^b | Velakoulis, Dennis^d | Desmond, Patricia^e | Hicks, Rodney J.^{e; f} | Zetterberg, Henrik^{g; h; i; j} | Blennow, Kaj^{g; h} | O’Brien, Terence J.^{a; k}

Affiliations: [a] Department of Medicine, Royal Melbourne Hospital, VIC, Australia | [b] Melbourne School of Psychological Sciences, The University of Melbourne, VIC, Australia | [c] Developmental Imaging, Murdoch Children’s Research Institute, Melbourne, VIC, Australia | [d] Department of Psychiatry, University of Melbourne, VIC, Australia | [e] Department of Radiology, University of Melbourne, VIC, Australia | [f] Centre for Molecular Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia | [g] Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden | [h] Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden | [i] Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK | [j] UK Dementia Research Institute at UCL, London, UK | [k] Departments of Neuroscience and Neurology, The Central Clinical School and The Alfred Hospital, Monash University, Melbourne, VIC, Australia

Correspondence: [*] Correspondence to: Dr. Charles B. Malpas, Clinical Outcomes Research Unit (CORe), Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC 3010, Australia. E-mail: [email protected].

Abstract: The two cardinal pathologies of Alzheimer’s disease (AD) develop according to distinct anatomical trajectories. Cerebral tau-related pathology first accumulates in the mesial temporal region, while amyloid-related pathology first appears in neocortex. The eventual distributions of these pathologies reflect their anatomical origins. An implication is that the cardinal pathologies might exert preferential effects on the structurofunctional brain changes observed in AD. We investigated this hypothesis in 39 patients with dementia of the Alzheimer’s type. Interrelationships were analyzed between cerebrospinal fluid biomarkers of the cardinal pathologies, volumetric brain changes using magnetic resonance imaging, and brain metabolism using [18F]-FDG-PET. Amyloid-related pathology was preferentially associated with structurofunctional changes in the precuneus and lateral temporal regions. Tau-related pathology was not associated with changes in these regions. These findings support the hypothesis that tau- and amyloid-pathology exert differential effects on structurofunctional changes in the AD brain. These findings have implications for future therapeutic trials and hint at a more complex relationship between the cardinal pathologies and disruption of brain networks.

Keywords: Alzheimer’s disease, amyloid-β, cerebral glucose uptake, cerebrospinal fluid, cortical thickness, P-tau

DOI: 10.3233/JAD-170250

Journal: Journal of Alzheimer's Disease, vol. 62, no. 1, pp. 417-427, 2018