Rare neurovascular genetic and imaging markers across neurodegenerative diseases

ONDRI Investigators; Allison A Dilliott; Stephanie A Berberian; Kelly M Sunderland; Malcolm A Binns; Julia Zimmer; Miracle Ozzoude; Christopher J M Scott; Fuqiang Gao; Anthony E Lang; David P Breen; Maria C Tartaglia; Brian Tan; Richard H Swartz; Ekaterina Rogaeva; Michael Borrie; Elizabeth Finger; Corinne E Fischer; Andrew Frank; Morris Freedman; Sanjeev Kumar; Stephen Pasternak; Bruce G Pollock; Tarek K Rajji; David F Tang-Wai; Agessandro Abrahao; John Turnbull; Lorne Zinman; Leanne Casaubon; Dar Dowlatshahi; Ayman Hassan; Jennifer Mandzia; Demetrios Sahlas; Gustavo Saposnik; David Grimes; Connie Marras; Thomas Steeves; Mario Masellis; Sali M K Farhan; Robert Bartha; Sean Symons; Robert A Hegele; Sandra E Black; Joel Ramirez

doi:10.1002/alz.13316

Rare neurovascular genetic and imaging markers across neurodegenerative diseases

ONDRI Investigators, Allison A Dilliott^*, Stephanie A Berberian, Kelly M Sunderland, Malcolm A Binns, Julia Zimmer, Miracle Ozzoude, Christopher J M Scott, Fuqiang Gao, Anthony E Lang, David P Breen, Maria C Tartaglia, Brian Tan, Richard H Swartz, Ekaterina Rogaeva, Michael Borrie, Elizabeth Finger, Corinne E Fischer, Andrew Frank, Morris FreedmanSanjeev Kumar, Stephen Pasternak, Bruce G Pollock, Tarek K Rajji, David F Tang-Wai, Agessandro Abrahao, John Turnbull, Lorne Zinman, Leanne Casaubon, Dar Dowlatshahi, Ayman Hassan, Jennifer Mandzia, Demetrios Sahlas, Gustavo Saposnik, David Grimes, Connie Marras, Thomas Steeves, Mario Masellis, Sali M K Farhan, Robert Bartha, Sean Symons, Robert A Hegele, Sandra E Black, Joel Ramirez

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Journal	Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Early online date	5 Jun 2023
DOIs	https://doi.org/10.1002/alz.13316
Publication status	E-pub ahead of print - 5 Jun 2023

Access to Document

10.1002/alz.13316

Alzheimer s Dementia - 2023 - Dilliott - Rare neurovascular genetic and imaging markers across neurodegenerative diseasesFinal published version, 820 KBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Cite this

ONDRI Investigators, Dilliott, A. A., Berberian, S. A., Sunderland, K. M., Binns, M. A., Zimmer, J., Ozzoude, M., Scott, C. J. M., Gao, F., Lang, A. E., Breen, D. P., Tartaglia, M. C., Tan, B., Swartz, R. H., Rogaeva, E., Borrie, M., Finger, E., Fischer, C. E., Frank, A., ... Ramirez, J. (2023). Rare neurovascular genetic and imaging markers across neurodegenerative diseases. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Advance online publication. https://doi.org/10.1002/alz.13316

@article{dd06d465305946369971976261c0d136,

title = "Rare neurovascular genetic and imaging markers across neurodegenerative diseases",

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.",

author = "{ONDRI Investigators} and Dilliott, {Allison A} and Berberian, {Stephanie A} and Sunderland, {Kelly M} and Binns, {Malcolm A} and Julia Zimmer and Miracle Ozzoude and Scott, {Christopher J M} and Fuqiang Gao and Lang, {Anthony E} and Breen, {David P} and Tartaglia, {Maria C} and Brian Tan and Swartz, {Richard H} and Ekaterina Rogaeva and Michael Borrie and Elizabeth Finger and Fischer, {Corinne E} and Andrew Frank and Morris Freedman and Sanjeev Kumar and Stephen Pasternak and Pollock, {Bruce G} and Rajji, {Tarek K} and Tang-Wai, {David F} and Agessandro Abrahao and John Turnbull and Lorne Zinman and Leanne Casaubon and Dar Dowlatshahi and Ayman Hassan and Jennifer Mandzia and Demetrios Sahlas and Gustavo Saposnik and David Grimes and Connie Marras and Thomas Steeves and Mario Masellis and Farhan, {Sali M K} and Robert Bartha and Sean Symons and Hegele, {Robert A} and Black, {Sandra E} and Joel Ramirez",

note = "{\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2023",

month = jun,

day = "5",

doi = "10.1002/alz.13316",

language = "English",

journal = "Alzheimer's & Dementia: The Journal of the Alzheimer's Association",

issn = "1552-5260",

publisher = "Wiley",

}

ONDRI Investigators, Dilliott, AA, Berberian, SA, Sunderland, KM, Binns, MA, Zimmer, J, Ozzoude, M, Scott, CJM, Gao, F, Lang, AE, Breen, DP, Tartaglia, MC, Tan, B, Swartz, RH, Rogaeva, E, Borrie, M, Finger, E, Fischer, CE, Frank, A, Freedman, M, Kumar, S, Pasternak, S, Pollock, BG, Rajji, TK, Tang-Wai, DF, Abrahao, A, Turnbull, J, Zinman, L, Casaubon, L, Dowlatshahi, D, Hassan, A, Mandzia, J, Sahlas, D, Saposnik, G, Grimes, D, Marras, C, Steeves, T, Masellis, M, Farhan, SMK, Bartha, R, Symons, S, Hegele, RA, Black, SE & Ramirez, J 2023, 'Rare neurovascular genetic and imaging markers across neurodegenerative diseases', Alzheimer's & Dementia: The Journal of the Alzheimer's Association. https://doi.org/10.1002/alz.13316

TY - JOUR

T1 - Rare neurovascular genetic and imaging markers across neurodegenerative diseases

AU - ONDRI Investigators

AU - Dilliott, Allison A

AU - Berberian, Stephanie A

AU - Sunderland, Kelly M

AU - Binns, Malcolm A

AU - Zimmer, Julia

AU - Ozzoude, Miracle

AU - Scott, Christopher J M

AU - Gao, Fuqiang

AU - Lang, Anthony E

AU - Breen, David P

AU - Tartaglia, Maria C

AU - Tan, Brian

AU - Swartz, Richard H

AU - Rogaeva, Ekaterina

AU - Borrie, Michael

AU - Finger, Elizabeth

AU - Fischer, Corinne E

AU - Frank, Andrew

AU - Freedman, Morris

AU - Kumar, Sanjeev

AU - Pasternak, Stephen

AU - Pollock, Bruce G

AU - Rajji, Tarek K

AU - Tang-Wai, David F

AU - Abrahao, Agessandro

AU - Turnbull, John

AU - Zinman, Lorne

AU - Casaubon, Leanne

AU - Dowlatshahi, Dar

AU - Hassan, Ayman

AU - Mandzia, Jennifer

AU - Sahlas, Demetrios

AU - Saposnik, Gustavo

AU - Grimes, David

AU - Marras, Connie

AU - Steeves, Thomas

AU - Masellis, Mario

AU - Farhan, Sali M K

AU - Bartha, Robert

AU - Symons, Sean

AU - Hegele, Robert A

AU - Black, Sandra E

AU - Ramirez, Joel

PY - 2023/6/5

Y1 - 2023/6/5

N2 - 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.

AB - 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.

U2 - 10.1002/alz.13316

DO - 10.1002/alz.13316

M3 - Article

C2 - 37272523

SN - 1552-5260

JO - Alzheimer's & Dementia: The Journal of the Alzheimer's Association

JF - Alzheimer's & Dementia: The Journal of the Alzheimer's Association

ER -

Rare neurovascular genetic and imaging markers across neurodegenerative diseases

Abstract

Access to Document

Fingerprint

Cite this