Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy

Indira Garcia-Cordero; Chloe Anastassiadis; Abeer Khoja; Alonso Morales-Rivero; Simrika Thapa; Anna Vasilevskaya; Carly Davenport; Vishaal Sumra; Blas Couto; Namita Multani; Foad Taghdiri; Cassandra Anor; Karen Misquitta; Lawren Vandevrede; Hilary Heuer; David Tang-Wai; Bradford Dickerson; Alexander Pantelyat; Irene Litvan; Bradley Boeve; Julio C Rojas; Peter Ljubenkov; Edward Huey; Susan Fox; Gabor G Kovacs; Adam Boxer; Anthony Lang; M Carmela Tartaglia; 4‐R‐Tauopathy Neuroimaging Initiative Consortium, and the Alzheimer's Disease Neuroimaging Initiative

doi:10.1002/ana.26930

Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy

Ann Neurol. 2024 Apr 5. doi: 10.1002/ana.26930. Online ahead of print.

Authors

Indira Garcia-Cordero¹, Chloe Anastassiadis¹, Abeer Khoja^{2

3}, Alonso Morales-Rivero^{2

4}, Simrika Thapa¹, Anna Vasilevskaya¹, Carly Davenport¹, Vishaal Sumra¹, Blas Couto^{5

6

7}, Namita Multani¹, Foad Taghdiri¹, Cassandra Anor¹, Karen Misquitta¹, Lawren Vandevrede⁸, Hilary Heuer⁸, David Tang-Wai⁹, Bradford Dickerson¹⁰, Alexander Pantelyat¹¹, Irene Litvan¹², Bradley Boeve¹³, Julio C Rojas⁸, Peter Ljubenkov⁸, Edward Huey¹⁴, Susan Fox^{5

6}, Gabor G Kovacs^{1

5

6

9}, Adam Boxer⁸, Anthony Lang^{1

5

6

9}, M Carmela Tartaglia^{1

2

5

9}; 4‐R‐Tauopathy Neuroimaging Initiative Consortium, and the Alzheimer's Disease Neuroimaging Initiative

Affiliations

¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
² University Health Network Memory Clinic, Toronto, ON, Canada.
³ Neurology Division, Medical Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ ABC Medical Center, Mexico City, Mexico.
⁵ Rossy PSP Program, University Health Network and the University of Toronto, Toronto, ON, Canada.
⁶ The Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic, Toronto, ON, Canada.
⁷ Institute of Cognitive and Translational Neuroscience (INCyT-INECO-CONICET), Favaloro University Hospital, Buenos Aires, Argentina.
⁸ Memory and Aging Center, Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA.
⁹ Krembil Brain Institute, University Health Network, Toronto, ON, Canada.
¹⁰ Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹¹ Department of Neurology, John Hopkins University, Baltimore, MD, USA.
¹² Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.
¹³ Department of Neurology, Mayo Clinic, Rochester, MN, USA.
¹⁴ Department of Psychiatry and Human Behavior, Brown University, Providence, RI, USA.

PMID: 38578117
DOI: 10.1002/ana.26930

Abstract

Objectives: To evaluate the effect of Alzheimer's disease (AD) -related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP).

Methods: Data from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4-R-Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD-positive (CBS/PSP-AD) and AD-negative (CBS/PSP-noAD) groups based on fluid biomarkers and amyloid PET scans. Cognitive, motor, and depression scores; AD fluid biomarkers (cerebrospinal p-tau, t-tau, and amyloid-beta, and plasma ptau-217); and neuroimaging data (amyloid PET, MRI and fMRI) were collected. Clinical features, whole-brain gray matter volume and functional networks connectivity were compared across groups.

Results: Data were analyzed from 87 CBS/PSP-noAD and 23 CBS/PSP-AD, 18 AD, and 30 healthy controls. CBS/PSP-noAD showed worse performance in comparison to CBS/PSP-AD in the PSPRS [mean(SD): 34.8(15.8) vs 23.3(11.6)] and the UPDRS scores [mean(SD): 34.2(17.0) vs 21.8(13.3)]. CBS/PSP-AD demonstrated atrophy in AD signature areas and brainstem, while CBS/PSP-noAD patients displayed atrophy in frontal and temporal areas, globus pallidus, and brainstem compared to healthy controls. The default mode network showed greatest disconnection in CBS/PSP-AD compared with CBS/PSP-no AD and controls. The thalamic network connectivity was most affected in CBS/PSP-noAD.

Interpretation: AD biomarker positivity may modulate the clinical presentation of CBS/PSP, with evidence of distinctive structural and functional brain changes associated with the AD pathology/co-pathology. ANN NEUROL 2024.

Abstract

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