Abstract
Genetic polymorphisms like apolipoprotein E (APOE) and microtubule-associated protein tau (MAPT) genes increase the risk of neurodegeneration. 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. 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. 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. 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.
Highlights
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease believed to be associated with repetitive head impacts
The remaining 29 participants were examined for the presence of Alzheimer's disease (AD)-like pattern on magnetic resonance imaging (MRI) i.e. medial temporal atrophy and/or precuneus/posterior cingulate atrophy and on positron emission tomography (PET) [F18]AV-1451 standard uptake value ratios (SUVRs) for increased tracer uptake in middle temporal lobe and posterior cortical regions including parietal lobe, and no such pattern was seen
This is the first study to examine the relationship between apolipoprotein E (APOE), microtubule-associated protein tau (MAPT) and cortical tau burden as seen with PET [F18]AV-1451 imaging in a cohort of former professional and semi-professional sport athletes with multiple concussions or sub-concussive hits at risk of delayed neurodegeneration, CTE
Summary
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease believed to be associated with repetitive head impacts. One study reported mildly elevated PET tau binding in two out of nine amyloid negative patients at risk for CTE, with the distribution pattern consistent with CTE pathology stages III-IV. The APOE4 allele has been associated with elevated postconcussion symptoms in military veterans [Merritt et al, 21], and increased phosphorylated tau levels in the brains of a blast-injury mouse model [Cao et al, 12]. This provides limited, but possible evidence for an association between APOE and tau pathology in TBI cases. This study examines the effect of the APOE4 allele and MAPT H1H1 on SUVRs of PET tau-specific [F-18]AV-1451 tracer in former professional contact sport athletes at risk for CTE. The cerebellar grey matter was used as the reference region
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