Interaction of APOE4 alleles and PET tau imaging in former contact sport athletes

Anna Vasilevskaya; Foad Taghdiri; Charles Burke; Apameh Tarazi; Seyed Ali Naeimi; Mozghan Khodadadi; Ruma Goswami; Christine Sato; Mark Grinberg; Danielle Moreno; Richard Wennberg; David Mikulis; Robin Green; Brenda Colella; Karen D Davis; Pablo Rusjan; Sylvain Houle; Charles Tator; Ekaterina Rogaeva; Maria C Tartaglia

doi:10.1016/j.nicl.2020.102212

Interaction of APOE4 alleles and PET tau imaging in former contact sport athletes

Neuroimage Clin. 2020:26:102212. doi: 10.1016/j.nicl.2020.102212. Epub 2020 Feb 13.

Authors

Anna Vasilevskaya¹, Foad Taghdiri², Charles Burke³, Apameh Tarazi⁴, Seyed Ali Naeimi⁵, Mozghan Khodadadi⁵, Ruma Goswami⁵, Christine Sato⁶, Mark Grinberg⁶, Danielle Moreno⁶, Richard Wennberg⁴, David Mikulis⁷, Robin Green⁸, Brenda Colella⁹, Karen D Davis¹⁰, Pablo Rusjan¹¹, Sylvain Houle¹¹, Charles Tator¹², Ekaterina Rogaeva¹³, Maria C Tartaglia¹⁴

Affiliations

¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard avenue, Toronto, ON M5T 0S8, Canada; Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Division of Neurology, Toronto Western Hospital, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada.
² Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard avenue, Toronto, ON M5T 0S8, Canada; Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada.
³ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard avenue, Toronto, ON M5T 0S8, Canada; Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Division of Neurology, Toronto Western Hospital, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; School of Medicine & Dentistry, Western University, Windsor, ON, Canada.
⁴ Division of Neurology, Toronto Western Hospital, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada.
⁵ Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada.
⁶ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard avenue, Toronto, ON M5T 0S8, Canada.
⁷ Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Division of Neuroradiology, Joint Department of Medical Imaging, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada.
⁸ Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Department of Rehabilitation Sciences, University of Toronto, 500 University Ave, Toronto, ON, M5G 1V7, Canada.
⁹ Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Department of Rehabilitation Sciences, University of Toronto, 500 University Ave, Toronto, ON, M5G 1V7, Canada.
¹⁰ Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Department of Surgery, University of Toronto, 149 College St., Toronto, ON, M5T 1P5, Canada.
¹¹ Research Imaging Centre, Campbell Research Institute, Centre for Addiction and Mental Health, 250 College St., Toronto, ON, M5T 1R8, Canada.
¹² Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Division of Neurosurgery, Toronto Western Hospital, Krembil Brain Institute, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada.
¹³ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard avenue, Toronto, ON M5T 0S8, Canada; Department of Medicine, Division of Neurology, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
¹⁴ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard avenue, Toronto, ON M5T 0S8, Canada; Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada; Division of Neurology, Toronto Western Hospital, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada; Canadian Concussion Center, Toronto Western Hospital, Krembil Neuroscience Centre, University Health Network, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada. Electronic address: carmela.tartaglia@uhn.ca.

Abstract

Background: Genetic polymorphisms like apolipoprotein E (APOE) and microtubule-associated protein tau (MAPT) genes increase the risk of neurodegeneration.

Methods: 38 former players (age 52.63±14.02) of contact sports underwent neuroimaging, biofluid collection, and comprehensive neuropsychological assessment. The [F-18]AV-1451 tracer signal was compared in the cortical grey matter between APOE4 allele carriers and non-carriers as well as carriers of MAPT H1H1 vs non-H1H1. Participants were then divided into the high (N = 13) and low (N = 13) groups based on cortical PET tau standard uptake value ratios (SUVRs) for comparison.

Findings: Cortical grey matter PET tau SUVR values were significantly higher in APOE4 carriers compared to non-carriers (p = 0.020). In contrast, there was no significant difference in SUVR between MAPT H1H1 vs non-H1H1 carrier genes (p = 1.00). There was a significantly higher APOE4 allele frequency in the high cortical grey matter PET tau group, comparing to low cortical grey matter PET tau group (p = 0.048). No significant difference in neuropsychological function was found between APOE4 allele carriers and non-carriers.

Interpretation: There is an association between higher cortical grey matter tau burden as seen with [F-18]AV-1451 PET tracer SUVR, and the APOE4 allele in former professional and semi-professional players at high risk of concussions. APOE4 allele may be a risk factor for tau accumulation in former contact sports athletes at high risk of neurodegeneration.

Funding: Toronto General and Western Hospital Foundations; Weston Brain Institute; Canadian Consortium on Neurodegeneration in ageing; Krembil Research Institute. There was no role of the funders in this study.

Keywords: Apoe4; Chronic traumatic encephalopathy; Concussion; Positron emission tomography; Tau.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Alleles
Apolipoprotein E4 / genetics*
Athletes
Athletic Injuries / genetics*
Athletic Injuries / pathology
Brain / pathology*
Canada
Chronic Traumatic Encephalopathy / genetics*
Female
Genetic Predisposition to Disease / genetics*
Gray Matter / metabolism
Gray Matter / pathology
Heterozygote
Humans
Male
Middle Aged
Positron-Emission Tomography
tau Proteins / genetics*

Substances

Apolipoprotein E4
MAPT protein, human
tau Proteins