Rare neurovascular genetic and imaging markers across neurodegenerative diseases

Allison A Dilliott¹, Stephanie A Berberian², Kelly M Sunderland³, Malcolm A Binns^{3

4}, Julia Zimmer¹, Miracle Ozzoude^{2

5}, Christopher J M Scott², Fuqiang Gao², Anthony E Lang⁶, David P Breen⁷, Maria C Tartaglia^{6

8}, Brian Tan³, Richard H Swartz^{2

9

10}, Ekaterina Rogaeva⁵, Michael Borrie^{11

12}, Elizabeth Finger¹¹, Corinne E Fischer¹³, Andrew Frank^{14

15}, Morris Freedman^{3

16}, Sanjeev Kumar^{17

18}, Stephen Pasternak¹⁹, Bruce G Pollock^{17

18}, Tarek K Rajji^{17

18

20}, David F Tang-Wai⁹, Agessandro Abrahao⁹, John Turnbull²¹, Lorne Zinman⁹, Leanne Casaubon⁹, Dar Dowlatshahi¹⁴, Ayman Hassan²², Jennifer Mandzia¹¹, Demetrios Sahlas²¹, Gustavo Saposnik^{23

24}, David Grimes¹⁴, Connie Marras⁶, Thomas Steeves²⁴, Mario Masellis^{2

9}, Sali M K Farhan¹, Robert Bartha¹⁹, Sean Symons²⁵, Robert A Hegele¹⁹, Sandra E Black^{2

3

9

10}, Joel Ramirez²; ONDRI Investigators

Affiliations

¹ Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec, Canada.
² Dr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
³ Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
⁴ Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁵ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
⁶ Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, Ontario, Canada.
⁷ Centre for Clinical Brain Sciences, University of Edinburgh; Anne Rowling Regenerative Neurology Clinic, University of Edinburgh; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
⁸ Division of Neurology, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
⁹ Department of Medicine (Neurology), Sunnybrook Health Sciences and University of Toronto, Ontario, Canada.
¹⁰ Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
¹¹ Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
¹² St. Joseph's Healthcare Centre, London, Ontario, Canada.
¹³ Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.
¹⁴ Department of Medicine (Neurology), University of Ottawa Brain and Mind Research Institute and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
¹⁵ Bruyère Research Institute, Ottawa, Ontario, Canada.
¹⁶ Department of Medicine (Neurology), Baycrest Health Sciences, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
¹⁷ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
¹⁸ Adult Neurodevelopment and Geriatric Psychiatry, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
¹⁹ Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
²⁰ Toronto Dementia Research Alliance, University of Toronto, Toronto, Ontario, Canada.
²¹ Division of Neurology, Department of Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Canada.
²² Thunder Bay Regional Health Research Institute, Thunder Bay, Ontario, Canada.
²³ Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
²⁴ Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
²⁵ Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

PMID: 37272523
DOI: 10.1002/alz.13316

Rare neurovascular genetic and imaging markers across neurodegenerative diseases

Allison A Dilliott et al. Alzheimers Dement. 2023 Dec.

. 2023 Dec;19(12):5583-5595.

doi: 10.1002/alz.13316. Epub 2023 Jun 5.

Authors

Affiliations

¹ Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montréal, Quebec, Canada.
² Dr. Sandra Black Centre for Brain Resilience and Recovery, LC Campbell Cognitive Neurology, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario, Canada.
³ Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada.
⁴ Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
⁵ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
⁶ Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, Toronto, Ontario, Canada.
⁷ Centre for Clinical Brain Sciences, University of Edinburgh; Anne Rowling Regenerative Neurology Clinic, University of Edinburgh; Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
⁸ Division of Neurology, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
⁹ Department of Medicine (Neurology), Sunnybrook Health Sciences and University of Toronto, Ontario, Canada.
¹⁰ Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
¹¹ Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
¹² St. Joseph's Healthcare Centre, London, Ontario, Canada.
¹³ Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada.
¹⁴ Department of Medicine (Neurology), University of Ottawa Brain and Mind Research Institute and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
¹⁵ Bruyère Research Institute, Ottawa, Ontario, Canada.
¹⁶ Department of Medicine (Neurology), Baycrest Health Sciences, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
¹⁷ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
¹⁸ Adult Neurodevelopment and Geriatric Psychiatry, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
¹⁹ Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
²⁰ Toronto Dementia Research Alliance, University of Toronto, Toronto, Ontario, Canada.
²¹ Division of Neurology, Department of Medicine, Hamilton Health Sciences, McMaster University, Hamilton, Canada.
²² Thunder Bay Regional Health Research Institute, Thunder Bay, Ontario, Canada.
²³ Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
²⁴ Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
²⁵ Department of Medical Imaging, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

PMID: 37272523
DOI: 10.1002/alz.13316

Abstract

Introduction: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status.

Methods: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1).

Results: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood.

Discussion: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.

Keywords: HTRA1; NOTCH3; ONDRI; WMH; neurodegeneration; small vessel disease.

PubMed Disclaimer

References

REFERENCES

1. Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010;9(1474-4465):689-701. Electronic.
1. Wardlaw JM, Smith EE, Biessels GJ, et al. Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013;12(8):822-838.
1. Cai Z, Wang C, He W, et al. Cerebral small vessel disease and Alzheimer's disease. Clin Interv Aging. 2015;10:1695-1704. doi:10.2147/CIA.S90871
1. Yoshita M, Fletcher E, Harvey D, et al. Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD. Neurology. 2006;67(12):2192-2198.
1. Ramirez J, Berezuk C, McNeely AA, Scott CJM, Gao F, Black SE. Visible Virchow-Robin spaces on magnetic resonance imaging of Alzheimer's disease patients and normal elderly from the Sunnybrook dementia study. J Alzheimer's Dis 2015;43(2):415-424. doi:10.3233/JAD-132528

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Ovid Technologies, Inc.
- Wiley
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Rare neurovascular genetic and imaging markers across neurodegenerative diseases

Affiliations

Rare neurovascular genetic and imaging markers across neurodegenerative diseases

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous