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

Accepted version
Peer-reviewed

Type

Article

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Authors

Savulich, George 
Jones, P Simon 
Street, Duncan 

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 (BPND), AD-tau pathology by [18F]AV-1451 BPND, 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 BPND 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.

Description

Keywords

Alzheimer's disease, CBD/PSP, corticobasal syndrome, synaptic loss, β‐amyloid status, Humans, Male, Female, Aged, Amyloid beta-Peptides, Middle Aged, Positron-Emission Tomography, Synapses, Corticobasal Degeneration, tau Proteins, Magnetic Resonance Imaging, Gray Matter, Alzheimer Disease, Cognitive Dysfunction, Carbolines

Journal Title

Mov Disord

Conference Name

Journal ISSN

0885-3185
1531-8257

Volume Title

Publisher

Wiley
Sponsorship
Wellcome Trust (220258/Z/20/Z)
MRC (MC_UU_00030/14)
MRC (via University of Oxford) (MR/T033371/1)
MRC (via University of Oxford) (Unknown)
Patrick Berthoud Charitable Trust (via Charities Aid Foundation) (Unknown)