Differential Synaptic Loss in β-Amyloid Positive Versus β-Amyloid Negative Corticobasal Syndrome

Negin Holland; George Savulich; P Simon Jones; David J Whiteside; Duncan Street; Peter Swann; Michelle Naessens; Maura Malpetti; Young T Hong; Tim D Fryer; Timothy Rittman; Eoin Mulroy; Franklin I Aigbirhio; Kailash P Bhatia; John T O'Brien; James B Rowe

doi:10.1002/mds.29814

Differential Synaptic Loss in β-Amyloid Positive Versus β-Amyloid Negative Corticobasal Syndrome

Mov Disord. 2024 Apr 26. doi: 10.1002/mds.29814. Online ahead of print.

Authors

Negin Holland^{1

2}, George Savulich³, P Simon Jones¹, David J Whiteside^{1

2}, Duncan Street¹, Peter Swann³, Michelle Naessens¹, Maura Malpetti¹, Young T Hong^{1

4}, Tim D Fryer^{1

4}, Timothy Rittman¹, Eoin Mulroy⁵, Franklin I Aigbirhio¹, Kailash P Bhatia⁵, John T O'Brien^{2

3}, James B Rowe^{1

2

6}

Affiliations

¹ Department of Clinical Neurosciences, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
² Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.
³ Department of Psychiatry, University of Cambridge, Cambridge Biomedical Campus, Cambridge, United Kingdom.
⁴ Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom.
⁵ Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, United Kingdom.
⁶ Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge, Cambridge, United Kingdom.

PMID: 38671545
DOI: 10.1002/mds.29814

Abstract

Background/objective: The corticobasal syndrome (CBS) is a complex asymmetric movement disorder, with cognitive impairment. Although commonly associated with the primary 4-repeat-tauopathy of corticobasal degeneration, clinicopathological correlation is poor, and a significant proportion is due to Alzheimer's disease (AD). Synaptic loss is a pathological feature of many clinical and preclinical tauopathies. We therefore measured the degree of synaptic loss in patients with CBS and tested whether synaptic loss differed according to β-amyloid status.

Methods: Twenty-five people with CBS, and 32 age-/sex-/education-matched healthy controls participated. Regional synaptic density was estimated by [¹¹C]UCB-J non-displaceable binding potential (BP_ND), AD-tau pathology by [¹⁸F]AV-1451 BP_ND, and gray matter volume by T1-weighted magnetic resonance imaging. Participants with CBS had β-amyloid imaging with ¹¹C-labeled Pittsburgh Compound-B ([¹¹C]PiB) positron emission tomography. Symptom severity was assessed with the progressive supranuclear palsy-rating-scale, the cortical basal ganglia functional scale, and the revised Addenbrooke's Cognitive Examination. Regional differences in BP_ND and gray matter volume between groups were assessed by ANOVA.

Results: Compared to controls, patients with CBS had higher [¹⁸F]AV-1451 uptake, gray matter volume loss, and reduced synaptic density. Synaptic loss was more severe and widespread in the β-amyloid negative group. Asymmetry of synaptic loss was in line with the clinically most affected side.

Discussion: Distinct patterns of [¹¹C]UCB-J and [¹⁸F]AV-1451 binding and gray matter volume loss, indicate differences in the pathogenic mechanisms of CBS according to whether it is associated with the presence of Alzheimer's disease or not. This highlights the potential for different therapeutic strategies in CBSs. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Keywords: Alzheimer's disease; CBD/PSP; corticobasal syndrome; synaptic loss; β‐amyloid status.

Abstract

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