Genetic Profile in Genes Associated with Sports Injuries in Elite Endurance Athletes.

Injuries are a complex trait that can stem from the interaction of several genes. The aim of this research was to examine the relationship between muscle performance-related genes and overuse injury risk in elite endurance athletes, and to examine the feasibility of determining a total genotype score that significantly correlates with injury. A cohort of 100 elite endurance athletes (50 male and 50 female) was selected. AMPD1 (rs17602729), ACE (rs4646994), ACTN3 (rs1815739), CKM (rs8111989) and MLCK ([rs2849757] and [rs2700352]) polymorphisms were genotyped by using real-time polymerase chain reaction (real time-PCR). Injury characteristics during the athletic season were classified following the Consensus Statement for injuries evaluation. The mean total genotype score (TGS) in non-injured athletes (68.263±13.197 arbitrary units [a.u.]) was different from that of injured athletes (50.037±17.293 a.u., p<0.001). The distribution of allelic frequencies in the AMPD1 polymorphism was also different between non-injured and injured athletes (p<0.001). There was a TGS cut-off point (59.085 a.u.) to discriminate non-injured from injured athletes with an odds ratio of 7.400 (95% CI 2.548-21.495, p<0.001). TGS analysis appears to correlate with elite endurance athletes at higher risk for injury. Further study may help to develop this as one potential tool to help predict injury risk in this population.

Improved recovery from skeletal muscle damage is largely unexplained by myofibrillar protein synthesis or inflammatory and regenerative gene expression pathways.

The contribution of myofibrillar protein synthesis (MyoPS) to recovery from skeletal muscle damage in humans is unknown. Recreationally active men and women consumed a daily protein-polyphenol beverage targeted at increasing amino acid availability and reducing inflammation (PPB; n = 9), both known to affect MyoPS, or an isocaloric placebo (PLA; n = 9) during 168 h of recovery from 300 maximal unilateral eccentric contractions (EE). Muscle function was assessed daily. Muscle biopsies were collected for 24, 27, 36, 72, and 168 h for MyoPS measurements using 2H2O and expression of 224 genes using RT-qPCR and pathway analysis. PPB improved recovery of muscle function, which was impaired for 5 days after EE in PLA (interaction P < 0.05). Acute postprandial MyoPS rates were unaffected by nutritional intervention (24-27 h). EE increased overnight (27-36 h) MyoPS versus the control leg (PLA: 33 ± 19%; PPB: 79 ± 25%; leg P < 0.01), and PPB tended to increase this further (interaction P = 0.06). Daily MyoPS rates were greater with PPB between 72 and 168 h after EE, albeit after function had recovered. Inflammatory and regenerative signaling pathways were dramatically upregulated and clustered after EE but were unaffected by nutritional intervention. These results suggest that accelerated recovery from EE is not explained by elevated MyoPS or suppression of inflammation.NEW & NOTEWORTHY The present study investigated the contribution of myofibrillar protein synthesis (MyoPS) and associated gene signaling to recovery from 300 muscle-damaging, eccentric contractions. Measured with 2H2O, MyoPS rates were elevated during recovery and observed alongside expression of inflammatory and regenerative signaling pathways. A nutritional intervention accelerated recovery; however, MyoPS and gene signaling were unchanged compared with placebo. These data indicate that MyoPS and associated signaling do not explain accelerated recovery from muscle damage.

Genetic variations associated with non-contact muscle injuries in sport: A systematic review.

INTRODUCTION: Non-contact muscle injuries (NCMI) account for a large proportion of sport injuries, affecting athletes' performance and career, team results and financial aspects. Recently, genetic factors have been attributed a role in the susceptibility of an athlete to sustain NCMI. However, data in this field are only just starting to emerge. OBJECTIVES: To review available knowledge of genetic variations associated with sport-related NCMI. METHODS: The databases Pubmed, Scopus, and Web of Science were searched for relevant articles published until February 2021. The records selected for review were original articles published in peer-reviewed journals describing studies that have examined NCMI-related genetic variations in adult subjects (17-60 years) practicing any sport. The data extracted from the studies identified were as follows: general information, and data on genetic polymorphisms and NCMI risk, incidence and recovery time and/or severity. RESULTS: Seventeen studies examining 47 genes and 59 polymorphisms were finally included. 29 polymorphisms affecting 25 genes were found significantly associated with NCMI risk, incidence, recovery time, and/or severity. These genes pertain to three functional categories: (i) muscle fiber structural/contractile properties, (ii) muscle repair and regeneration, or (iii) muscle fiber external matrix composition and maintenance. CONCLUSION: Our review confirmed the important role of genetics in NCMI. Some gene variants have practical implications such as differences of several weeks in recovery time detected between genotypes. Knowledge in this field is still in its early stages. Future studies need to examine a wider diversity of sports and standardize their methods and outcome measures.

Contralateral and siblings' knees are at higher risk of ACL tear for patients with a positive history of ACL tear.

PURPOSE: Recent studies have shown that several genetic factors can cause susceptibility to anterior cruciate ligament (ACL) rupture. The aim of the present study was to evaluate certain underlying factors that increase the risk of ACL rupture. METHODS: Eight hundred thirty-six patients with ACL rupture who underwent ACL reconstructive surgery from 2010 to 2013 at an academic center completed a minimum of 5 years post-operation follow-up. The collected variables included sex, age, height, weight, exercise level, time interval between ACL rupture in the first knee and contralateral ACL rupture, dominant leg, side of the involved knee and sibling history of ACL rupture. RESULTS: The median follow-up duration was 6.5 (range: 5-8) years. Eighty-three patients (9.9%) had a contralateral ACL rupture, and 155 patients (18.5%) had siblings with a history of ACL rupture. The rate of contralateral ACL rupture was three times higher in women than in men and in patients with siblings with a history of ACL rupture than in those without such history. In addition, the risk of contralateral ACL rupture was higher in those younger than 30 years of age, those with a BMI of 20-25 kg/m2 and those who participated in regular sports activity. However, whether the involved knee was on the dominant or nondominant side had no effect on the incidence of contralateral ACL rupture. The results of the study showed that 69 (83.1%) of the contralateral ACL ruptures occurred within the first 2 years after the primary operation. CONCLUSION: In a 5- to 8-year follow-up, one out of every ten patients had a contralateral ACL rupture, and two out of every ten patients had siblings with a history of ACL rupture. The findings suggest that having a sibling with a history of ACL rupture and being female are important risk factors for ACL rupture of the contralateral knee. LEVEL OF EVIDENCE: III.

[Lower limb muscle injury prevention]. / Prévention des lésions musculaires des membres inférieurs.

Muscle injuries are one of the most common injuries in professional and recreational sports. Their impact on absence during the games is therefore major. There are many risk factors, the main ones being a previous muscle injury, a lack of strength in the muscle in question, and the age of the athlete. Preventive medicine in this field, although essential, remains perfectible and the various preventive measures are sometimes not fully studied, or present variable evidence. Stretching, neuro-muscular exercises, muscle strengthening, nutrition or genetics can all be part of the most comprehensive preventive possible approach.

Les lésions musculaires sont l'une des blessures les plus fréquentes dans la pratique sportive professionnelle et de loisir. Leur impact sur les absences de terrain est donc majeur. Les facteurs de risque sont nombreux, avec comme facteurs principaux un antécédent de lésion musculaire, un déficit de force du muscle considéré, ainsi que l'âge du sportif. La médecine préventive dans ce domaine, pourtant essentielle, reste encore perfectible et les différentes mesures de prévention sont parfois très peu étudiées, ou présentent des évidences variables. Le stretching, les exercices neuromusculaires, le renforcement musculaire, la nutrition ou la génétique peuvent tous participer à une approche préventive la plus globale possible.

COL5A1 rs12722 polymorphism is not associated with passive muscle stiffness and sports-related muscle injury in Japanese athletes.

BACKGROUND: Poor joint flexibility has been repeatedly proposed as a risk factor for muscle injury. The C-to-T polymorphism (rs12722) in the 3'-untranslated region of the collagen type V α1 chain gene (COL5A1) is reportedly associated with joint flexibility. Flexibility of a normal joint is largely determined by passive muscle stiffness, which is influenced by intramuscular collagenous connective tissues including type V collagen. The present study aimed to test the hypothesis that the COL5A1 rs12722 polymorphism influences joint flexibility via passive muscle stiffness, and is accordingly associated with the incidence of muscle injury. METHODS: In Study 1, we examined whether the rs12722 polymorphism is associated with joint flexibility and passive muscle stiffness in 363 healthy young adults. Joint flexibility was evaluated by passive straight-leg-raise and sit-and-reach tests, and passive muscle stiffness was measured using ultrasound shear wave elastography. In Study 2, the association of the rs12722 polymorphism with sports-related muscle injury was assessed in 1559 Japanese athletes. Muscle injury history and severity were assessed by a questionnaire. In both Study 1 and Study 2, the rs12722 C-to-T polymorphism in the COL5A1 was determined using the TaqMan SNP Genotyping Assay. RESULTS: Study 1 revealed that the rs12722 polymorphism had no significant effect on range of motion in passive straight-leg-raise and sit-and-reach tests. Furthermore, there was no significant difference in passive muscle stiffness of the hamstring among the rs12722 genotypes. In Study 2, rs12722 genotype frequencies did not differ between the muscle injury and no muscle injury groups. Moreover, no association was observed between rs12722 polymorphism and severity of muscle injury. CONCLUSIONS: The present study does not support the view that COL5A1 rs12722 polymorphism has a role as a risk factor for sports-related muscle injury, or that it is a determinant for passive muscle stiffness in a Japanese population.

The interactions of physical activity, exercise and genetics and their associations with bone mineral density: implications for injury risk in elite athletes.

Low bone mineral density (BMD) is established as a primary predictor of osteoporotic risk and can also have substantial implications for athlete health and injury risk in the elite sporting environment. BMD is a highly multi-factorial phenotype influenced by diet, hormonal characteristics and physical activity. The interrelationships between such factors, and a strong genetic component, suggested to be around 50-85% at various anatomical sites, determine skeletal health throughout life. Genome-wide association studies and case-control designs have revealed many loci associated with variation in BMD. However, a number of the candidate genes identified at these loci have no known associated biological function or have yet to be replicated in subsequent investigations. Furthermore, few investigations have considered gene-environment interactions-in particular, whether specific genes may be sensitive to mechanical loading from physical activity and the outcome of such an interaction for BMD and potential injury risk. Therefore, this review considers the importance of physical activity on BMD, genetic associations with BMD and how subsequent investigation requires consideration of the interaction between these determinants. Future research using well-defined independent cohorts such as elite athletes, who experience much greater mechanical stress than most, to study such phenotypes, can provide a greater understanding of these factors as well as the biological underpinnings of such a physiologically "extreme" population. Subsequently, modification of training, exercise or rehabilitation programmes based on genetic characteristics could have substantial implications in both the sporting and public health domains once the fundamental research has been conducted successfully.

More than a 'speed gene': ACTN3 R577X genotype, trainability, muscle damage, and the risk for injuries.

A common null polymorphism (rs1815739; R577X) in the gene that codes for α-actinin-3 (ACTN3) has been related to different aspects of exercise performance. Individuals who are homozygous for the X allele are unable to express the α-actinin-3 protein in the muscle as opposed to those with the RX or RR genotype. α-actinin-3 deficiency in the muscle does not result in any disease. However, the different ACTN3 genotypes can modify the functioning of skeletal muscle during exercise through structural, metabolic or signaling changes, as shown in both humans and in the mouse model. Specifically, the ACTN3 RR genotype might favor the ability to generate powerful and forceful muscle contractions. Leading to an overall advantage of the RR genotype for enhanced performance in some speed and power-oriented sports. In addition, RR genotype might also favor the ability to withstand exercise-induced muscle damage, while the beneficial influence of the XX genotype on aerobic exercise performance needs to be validated in human studies. More information is required to unveil the association of ACTN3 genotype with trainability and injury risk during acute or chronic exercise.

ACTN3 R577X Polymorphism Is Associated With the Incidence and Severity of Injuries in Professional Football Players.

OBJECTIVE: The ACTN3 R577X gene variant results in the absence of the α-actinin-3 protein in ∼18% of humans worldwide and has been associated with athletic performance and increased susceptibility to eccentric muscle damage. The aim of this study was to investigate the association between ACTN3 R577X variant and indirect muscle disorders/injuries in professional football players. DESIGN: A case-control, genotype-phenotype association study. INTERVENTION: Two hundred fifty-seven male professional Italian football players (from Serie A, Primavera, Allievi, and Giovanissimi; age = 21.2 ± 5.3 years) and 265 nonathletic controls were recruited for the study. Genomic DNA was extracted using a buccal swab, and the ACTN3 R577X genotype was performed using a PCR method. Structural-mechanical injuries and functional muscle disorders were collected from a subgroup of 169 football players during the period of 2009 to 2014. MAIN OUTCOME MEASURE: We hypothesized that the 577XX genotype would be associated with higher predisposition to muscle injuries (compared with the other genotypes). RESULTS: ACTN3 XX (α-actinin-3 deficiency) players had 2.66 higher odds for an injury incidence than their ACTN3 RR counterparts (95% confidence interval [CI]: 1.09-6.63, P = 0.02), whereas RX and RR players had similar injury incidence. Furthermore, ACTN3 XX players had 2.13 higher odds for having a severe injury compared with their RR counterparts (95% CI: 1.25-3.74, P = 0.0054), whereas RX individuals had 1.63 higher odds for having a severe injury compared with the RR players (95% CI: 1.10-2.40, P = 0.015). CONCLUSIONS: The ACTN3 R577X polymorphism is associated with the incidence and severity of muscle injuries in professional football players; players with the ACTN3 577XX genotype have higher odds of having muscle injuries than their RR counterparts. CLINICAL RELEVANCE: Discovering the complex relationship between gene variants and muscle injuries may assist coaches, physiologists, and the medical community to development tailored injury prevention program for football players, which could provide a new edge for successful competition.

Sports-related Concussion - Genetic Factors.

Genetic biomarkers have been evaluated for validity in predicting risk for sports-related concussion as well as prognosticating recovery from this injury. Research results from predominantly small-scale pilot studies thus far are mixed and preliminary findings have not been adequately replicated. Currently, the use of such genetic biomarkers should be considered investigational and not for routine clinical use.

Genetic polymorphisms associated with the risk of concussion in 1056 college athletes: a multicentre prospective cohort study.

BACKGROUND/AIM: To evaluate the association of genetic polymorphisms APOE, APOE G-219T promoter, microtubule associated protein(MAPT)/tau exon 6 Ser53Pro, MAPT/tau Hist47Tyr, IL-6572 G/C and IL-6RAsp358Ala with the risk of concussion in college athletes. METHODS: A 23-centre prospective cohort study of 1056 college athletes with genotyping was completed between August 2003 and December 2012. All athletes completed baseline medical and concussion questionnaires, and post-concussion data were collected for athletes with a documented concussion. RESULTS: The study cohort consisted of 1056 athletes of mean±SD age 19.7±1.5 years, 89.3% male, 59.4% Caucasian, 35.0% African-American, 5.6% other race. The athletes participated in American football, soccer, basketball, softball, men's wrestling and club rugby. A total of 133 (12.1% prevalence) concussions occurred during an average surveillance of 3 years per athlete. We observed a significant positive association between IL-6R CC (p=0.001) and a negative association between APOE4 (p=0.03) and the risk of concussion. Unadjusted and adjusted logistic regression analysis showed a significant association between IL-6R CC and concussion (OR 3.48; 95% CI 1.58 to 7.65; p=0.002) and between the APOE4 allele and concussion (OR 0.61; 95% CI 0.38 to 0.96; p=0.04), which persisted after adjustment for confounders. CONCLUSIONS: IL-6R CC was associated with a three times greater concussion risk and APOE4 with a 40% lower risk.

Two Genetic Variants Associated with Plantar Fascial Disorders.

Plantar fascial disorder is comprised of plantar fasciitis and plantar fibromatosis. Plantar fasciitis is the most common cause of heel pain, especially for athletes involved in running and jumping sports. Plantar fibromatosis is a rare fibrous hyperproliferation of the deep connective tissue of the foot. To identify genetic loci associated with plantar fascial disorders, a genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health including 21,624 cases of plantar fascial disorders and 80,879 controls. One indel (chr5:118704153:D) and one SNP (rs62051384) showed an association with plantar fascial disorders at genome-wide significance (p<5×10-8) with small effects (odds ratios=0.93 and 1.07 per allele, respectively). The indel chr5:118704153:D is located within TNFAIP8 (encodes a protein induced by TNF alpha) and rs62051384 is located within WWP2 (which is involved in proteasomal degradation). These DNA variants may be informative in explaining why some individuals are at higher risk for plantar fascial disorders than others.

Investigation of angiogenesis genes with anterior cruciate ligament rupture risk in a South African population.

The angiogenesis-signalling pathway is a physiological response after mechanical loading to promote matrix remodelling and thereby maintain tissue homeostasis. Studies have shown increased expression of angiogenic molecules in response to loading and in ruptured ligaments. Recently, polymorphisms within the vascular endothelial growth factor A (VEGFA) and kinase insert-domain receptor (KDR) genes were associated with risk of anterior cruciate ligament (ACL) ruptures and Achilles tendinopathy in Caucasian study groups. A case-control genetic association study was conducted on 100 controls and 98 participants with surgically-diagnosed ACL ruptures; of which 51 participants reported non-contact mechanism of injury (NON). All participants were genotyped for five functional polymorphisms: VEGFA (rs699947, rs1570360, rs2010963) and KDR (rs2071559, rs1870377). Haplotypes were inferred. In the male participants, the KDR rs2071559 AG genotype was significantly over-represented (P = 0.048, OR: 1.90, 95% CI: 1.00-3.59) in the controls. Furthermore, the GG genotype was significantly under-represented in the male controls compared to the male ACL group (P = 0.018, OR: 2.77, 95% CI: 1.17-6.55) and the male NON subgroup (P = 0.013, OR: 3.26, 95% CI: 1.24-8.58). Haplotype analysis implicated the KDR gene in all participants and in male participants separately. Collectively, these results implicate the angiogenesis-signalling pathway as a potentially key biological pathway contributing to ACL injury susceptibility.

Ethics of genetic testing and research in sport: a position statement from the Australian Institute of Sport.

As Australia's peak high-performance sport agency, the Australian Institute of Sport (AIS) has developed this position statement to address the implications of recent advances in the field of genetics and the ramifications for the health and well-being of athletes. Genetic testing has proven of value in the practice of clinical medicine. There are, however, currently no scientific grounds for the use of genetic testing for athletic performance improvement, sport selection or talent identification. Athletes and coaches should be discouraged from using direct-to-consumer genetic testing because of its lack of validation and replicability and the lack of involvement of a medical practitioner in the process. The transfer of genetic material or genetic modification of cells for performance enhancement is gene doping and should not be used on athletes. There are, however, valid roles for genetic research and the AIS supports genetic research which aims to enhance understanding of athlete susceptibility to injury or illness. Genetic research is only to be conducted after careful consideration of a range of ethical concerns which include the provision of adequate informed consent. The AIS is committed to providing leadership in delivering an ethical framework that protects the well-being of athletes and the integrity of sport, in the rapidly changing world of genomic science.

Genetic biomarkers in non-contact muscle injuries in elite soccer players.

PURPOSE: Damage to skeletal muscle necessitates regeneration to maintain proper muscle form and function. Interindividual differences in injury severity, recovery time, and injury rate could be explained by the presence of single nucleotide polymorphisms (SNPs) in genes involved in the reparation and regeneration of connective tissue . We wished to identify new genetic biomarkers that could help to prevent or minimize the risk of non-contact muscle injuries and are associated with a predisposition to developing muscle injuries. METHODS: Using allelic discrimination techniques, we analysed 12 SNPs in selected genes from the genomic DNA of 74 elite soccer players. RESULTS: SNPs in the hepatocyte growth factor (HGF) gene showed evidence of a statistically significant association with injury incidence, severity, and recovery time. SNPs in the SOX15 gene showed evidence of a statistically significant association with injury incidence. SNPs in the GEFT and LIF genes showed evidence of a statistically significant association with recovery time. CONCLUSIONS: Genetic profile could explain why some elite soccer players are predisposed to suffer more injuries than others and why they need more time to recover from a particular injury. SNPs in HGF genes have an important role as biomarkers of biological processes fragility within muscle injuries related to injury rate, severity, and long recovery time.

Is the Combination of COL1A1 Gene Polymorphisms a Marker of Injury Risk?

CONTEXT: The most commonly injured body part for skiing has been found to be the knee. The rupture of the anterior cruciate ligament (ACL) was the most frequent diagnosis. ACL ruptures are determined by several extrinsic and intrinsic risk factors including those that are hormonal, neuromuscular, anatomical, or genetic. OBJECTIVES: To examine the association of both COL1A1 rs1800012 (+1245G/T) and COL1A1 rs1107946 (-1997G/T) polymorphisms, individually and as haplotypes, with ACL ruptures in recreational Polish skiers. DESIGN: Genomic DNA was extracted from buccal cells donated by the subjects, and genotyping was carried out using real-time polymerase chain reaction. SETTINGS: University laboratory. PARTICIPANTS: 138 male recreational skiers with surgically diagnosed primary ruptures and 183 apparently healthy male recreational skiers not differing markedly in age or level of exposure to ACL injury. MAIN OUTCOME MEASURES: COL1A1 rs1800012 and COL1A1 rs1107946 polymorphisms. RESULTS: There were significant differences in genotype distribution of the COL1A1 rs1800012 polymorphism between the ACL rupture group and the control group. The GG homozygotes were underrepresented in the ACL rupture group compared with the control group. There were no significant differences in genotype distribution or allele frequency of COL1A1 rs1107946 polymorphisms between the ACL rupture group and the control group. The G-G (COL1A1 rs1800012G and COL1A1 rs1107946G) haplotype was the most common. There were no significant differences in haplotype distribution between the ACL-rupture and control groups. CONCLUSION: The study showed that GG homozygotes were underrepresented in the ACL-rupture group compared with the control group, which suggests an association with reduced risk of ACL injury.

Genetic variation in SLC17A7 promoter associated with response to sport-related concussions.

OBJECTIVE: To determine the association of the single nucleotide polymorphism (SNP) rs74174284 within SLC17A7 promoter with concussion severity or duration. DESIGN: A between-subjects design was utilized. METHODS: Saliva samples and concussion severity and duration data were collected from 40 athletes diagnosed with a sport-related concussion by a physician, utilizing a standardized concussion assessment protocol. DNA was extracted, estimated and genotyped. RESULTS: An association was found between the dominant genetic model (CC vs GG + GC; p = 0.0179) and recovery, where those carrying the minor allele were 6.33-times more likely to experience prolonged recovery rates. Within the ImPACT assessment, those carrying the CC genotype (33.38 ± 10.15, p = 0.01) had worse motor speed scores upon initial assessment compared to both heterozygous (CG) and homozygous (GG) genotypes (41.59 ± 7.39). CONCLUSIONS: This study was the first to demonstrate an association between genetic polymorphism at rs7417284 SNP in the promoter region of the SLC17A7 gene and concussion severity and duration. Based upon these findings, rs74174284 is a potential predictive genetic marker for identifying athletes who are more susceptible for altered recovery times and worse motor speed ImPACT scores after sport-related concussion.

Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank.

Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.

Beta-amyloid deposition in chronic traumatic encephalopathy.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid ß peptide (Aß) levels, the extent of Aß deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Aß deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Aß deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Aß deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p < 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Aß plaques and those without. Aß deposition was significantly associated with the presence of the APOE ε4 allele (p = 0.035), older age at symptom onset (p < 0.001), and older age at death (p < 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (ß = 2.43, p = 0.018), co-morbid Lewy body disease (OR = 5.01, p = 0.009), and dementia (OR = 4.45, p = 0.012). A subset of subjects met the diagnostic criteria for both CTE and AD, and in these subjects both Aß plaques and total levels of Aß1-40 were increased at the depths of the cortical sulcus compared to the gyral crests. Overall, these findings suggest that Aß deposition is altered and accelerated in a cohort of CTE subjects compared to normal aging and that Aß is associated with both pathological and clinical progression of CTE independent of age.