Investigating the use of plasma pTau181 in retired contact sports athletes.
Athletes
CTE
Chronic traumatic encephalopathy
Concussion
Neurodegeneration
Plasma
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
05
02
2022
accepted:
09
06
2022
revised:
26
05
2022
pubmed:
26
6
2022
medline:
15
9
2022
entrez:
25
6
2022
Statut:
ppublish
Résumé
Considering the wide range of outcomes following sport-related concussions, biomarkers are needed to detect underlying pathological changes. The objective was to analyze the use of plasma phosphorylated tau 181 (pTau181) as a non-invasive measure of underlying brain changes in a cohort of retired contact sports athletes at risk of neurodegeneration. Fifty-four retired contact sport athletes and 27 healthy controls whose blood plasma was analyzed for pTau181 were included. A portion (N = 21) of retired athletes had a 2-years follow-up visit. All participants had completed a neuropsychological battery and MRI imaging. Plasma pTau181 was significantly higher in retired athletes compared to healthy controls (8.94 ± 5.08 pg/mL vs. 6.00 ± 2.53 pg/mL, respectively; 95% BCa CI 1.38-4.62; p = 0.02); and was significantly associated with fornix fractional anisotropy values only in the athletes group (β = - 0.002; 95% BCa CI - 0.003 to - 0.001; p = 0.002). When the retired athletes cohort was divided into high vs. normal pTau181 groups, the corpus callosum (CC) volume and white-matter integrity was significantly lower in high pTau181 compared to older healthy controls (CC volume: 1.57 ± 0.19 vs. 2.02 ± 0.32, p = 0.002; CC medial diffusivity: 0.96 ± 0.04 × 10 Although high plasma pTau181 levels were associated with abnormalities in CC and fornix, baseline pTau181 did not predict longitudinal changes in regional brain volumes or white-matter integrity in the athletes. pTau181 may be useful for identifying those with brain abnormalities related to repeated concussion but not for predicting progression.
Sections du résumé
BACKGROUND
BACKGROUND
Considering the wide range of outcomes following sport-related concussions, biomarkers are needed to detect underlying pathological changes. The objective was to analyze the use of plasma phosphorylated tau 181 (pTau181) as a non-invasive measure of underlying brain changes in a cohort of retired contact sports athletes at risk of neurodegeneration.
METHODS
METHODS
Fifty-four retired contact sport athletes and 27 healthy controls whose blood plasma was analyzed for pTau181 were included. A portion (N = 21) of retired athletes had a 2-years follow-up visit. All participants had completed a neuropsychological battery and MRI imaging.
RESULTS
RESULTS
Plasma pTau181 was significantly higher in retired athletes compared to healthy controls (8.94 ± 5.08 pg/mL vs. 6.00 ± 2.53 pg/mL, respectively; 95% BCa CI 1.38-4.62; p = 0.02); and was significantly associated with fornix fractional anisotropy values only in the athletes group (β = - 0.002; 95% BCa CI - 0.003 to - 0.001; p = 0.002). When the retired athletes cohort was divided into high vs. normal pTau181 groups, the corpus callosum (CC) volume and white-matter integrity was significantly lower in high pTau181 compared to older healthy controls (CC volume: 1.57 ± 0.19 vs. 2.02 ± 0.32, p = 0.002; CC medial diffusivity: 0.96 ± 0.04 × 10
CONCLUSIONS
CONCLUSIONS
Although high plasma pTau181 levels were associated with abnormalities in CC and fornix, baseline pTau181 did not predict longitudinal changes in regional brain volumes or white-matter integrity in the athletes. pTau181 may be useful for identifying those with brain abnormalities related to repeated concussion but not for predicting progression.
Identifiants
pubmed: 35751688
doi: 10.1007/s00415-022-11223-7
pii: 10.1007/s00415-022-11223-7
doi:
Substances chimiques
tau Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5582-5595Subventions
Organisme : Swedish Research Council
ID : 2018-02532
Organisme : the European Research Council
ID : 681712
Organisme : Swedish State Support for Clinical Research
ID : ALFGBG-720931
Organisme : the Alzheimer Drug Discovery Foundation
ID : 201809-2016862
Organisme : the AD Strategic Fund and the Alzheimer's Association
ID : ADSF-21-831376-C
Organisme : the AD Strategic Fund and the Alzheimer's Association
ID : ADSF-21-831381-C
Organisme : the AD Strategic Fund and the Alzheimer's Association
ID : ADSF-21-831377-C
Organisme : Hjärnfonden
ID : FO2019-0228
Organisme : Hjärnfonden
ID : FO2017-0243
Organisme : Hjärnfonden
ID : FO2020-0240
Organisme : Swedish Research Council
ID : 2017-00915
Organisme : Alzheimer's Drug Discovery Foundation
ID : RDAPB-201809-2016615
Organisme : Alzheimerfonden
ID : AF-742881
Organisme : Alzheimerfonden
ID : AF-930627
Organisme : the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement
ID : ALFGBG-715986
Organisme : the European Union Joint Program for Neurodegenerative Disorders
ID : JPND2019-466-236
Organisme : National Institute of Health
ID : 1R01AG068398-01
Organisme : BrightFocus Foundation
ID : A2020812F
Organisme : Agneta Prytz-Folkes och Gösta Folkes Stiftelse
ID : 2020-00124
Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
Références
Manley G, Gardner AJ, Schneider KJ, Guskiewicz KM, Bailes J, Cantu RC et al (2017) A systematic review of potential long-term effects of sport-related concussion. Br J Sports Med 51:969–977
pubmed: 28455362
doi: 10.1136/bjsports-2017-097791
Mez J, Daneshvar DH, Kiernan PT, Abdolmohammadi B, Alvarez VE, Huber BR et al (2017) Clinicopathological evaluation of chronic traumatic encephalopathy in players of american football. JAMA 318:360–370
pubmed: 28742910
pmcid: 5807097
doi: 10.1001/jama.2017.8334
Schwab N, Wennberg R, Grenier K, Tartaglia C, Tator C, Hazrati L-N (2021) Association of position played and career duration and chronic traumatic encephalopathy at autopsy in elite football and hockey players. Neurology. Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://n.neurology.org/content/early/2021/02/24/WNL.0000000000011668
Costello DM, Kaye AH, O’Brien TJ, Shultz SR (2018) Sport related concussion—potential for biomarkers to improve acute management. J Clin Neurosci 56:1–6
pubmed: 30055944
doi: 10.1016/j.jocn.2018.07.002
Oliver JM, Jones MT, Kirk KM, Gable DA, Repshas JT, Johnson TA et al (2016) Serum neurofilament light in American football athletes over the course of a season. J Neurotrauma 33:1784–1789 (Mary Ann Liebert, Inc. 140 Huguenot Street, 3rd Floor New Rochelle, NY 10801 USA)
pubmed: 26700106
doi: 10.1089/neu.2015.4295
Shahim P, Zetterberg H, Tegner Y, Blennow K (2017) Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports. Neurology 88:1788–1794
pubmed: 28404801
pmcid: 5419986
doi: 10.1212/WNL.0000000000003912
Shahim P, Tegner Y, Marklund N, Blennow K, Zetterberg H (2018) Neurofilament light and tau as blood biomarkers for sports-related concussion. Neurology 90:e1780–e1788
pubmed: 29653990
pmcid: 5957307
doi: 10.1212/WNL.0000000000005518
Taghdiri F, Multani N, Ozzoude M, Tarazi A, Khodadadi M, Wennberg R et al (2020) Neurofilament-light in former athletes: a potential biomarker of neurodegeneration and progression. Eur J Neurol 27:1170–1177
pubmed: 32281206
doi: 10.1111/ene.14251
Mielke MM, Hagen CE, Xu J, Chai X, Vemuri P, Lowe VJ et al (2018) Plasma phospho-tau181 increases with Alzheimer’s disease clinical severity and is associated with tau-and amyloid-positron emission tomography. Alzheimer’s Dementia 14:989–997
pubmed: 29626426
doi: 10.1016/j.jalz.2018.02.013
Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL et al (2020) Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol 19:422–433
pubmed: 32333900
doi: 10.1016/S1474-4422(20)30071-5
Thijssen EH, La Joie R, Wolf A, Strom A, Wang P, Iaccarino L et al (2020) Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration. Nat Med 26:387–397
pubmed: 32123386
pmcid: 7101073
doi: 10.1038/s41591-020-0762-2
Karikari TK, Benedet AL, Ashton NJ, Lantero Rodriguez J, Snellman A, Suárez-Calvet M et al (2021) Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s Disease Neuroimaging Initiative. Mol Psychiatry 26:429–442
pubmed: 33106600
doi: 10.1038/s41380-020-00923-z
Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Rodriguez JL, Snellman A et al (2021) Time course of phosphorylated-tau181 in blood across the Alzheimer’s disease spectrum. Brain 144:325–339
pubmed: 33257949
doi: 10.1093/brain/awaa399
Janelidze S, Mattsson N, Palmqvist S, Smith R, Beach TG, Serrano GE et al (2020) Plasma P-tau181 in Alzheimer’s disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer’s dementia. Nat Med 26:379–386
pubmed: 32123385
doi: 10.1038/s41591-020-0755-1
Lantero Rodriguez J, Karikari TK, Suárez-Calvet M, Troakes C, King A, Emersic A et al (2020) Plasma p-tau181 accurately predicts Alzheimer’s disease pathology at least 8 years prior to post-mortem and improves the clinical characterisation of cognitive decline. Acta Neuropathol 140:267–278
pubmed: 32720099
pmcid: 7423866
doi: 10.1007/s00401-020-02195-x
Ashton NJ, Pascoal TA, Karikari TK, Benedet AL, Lantero-Rodriguez J, Brinkmalm G et al (2021) Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology. Acta Neuropathol 141:709–724
pubmed: 33585983
pmcid: 8043944
doi: 10.1007/s00401-021-02275-6
Moscoso A, Grothe MJ, Ashton NJ, Karikari TK, Lantero Rodríguez J, Snellman A et al (2021) Longitudinal associations of blood phosphorylated Tau181 and neurofilament light chain with neurodegeneration in Alzheimer disease. JAMA Neurol 78:396–406
pubmed: 33427873
doi: 10.1001/jamaneurol.2020.4986
Simrén J, Leuzy A, Karikari TK, Hye A, Benedet AL, Lantero-Rodriguez J et al (2021) The diagnostic and prognostic capabilities of plasma biomarkers in Alzheimer’s disease. Alzheimers Dement 17(7):1145–1156
pubmed: 33491853
pmcid: 8359457
doi: 10.1002/alz.12283
Clark C, Lewczuk P, Kornhuber J, Richiardi J, Maréchal B, Karikari TK et al (2021) Plasma neurofilament light and phosphorylated tau 181 as biomarkers of Alzheimer’s disease pathology and clinical disease progression. Alzheimers Res Ther 13:65
pubmed: 33766131
pmcid: 7995778
doi: 10.1186/s13195-021-00805-8
Arena JD, Smith DH, Lee EB, Gibbons GS, Irwin DJ, Robinson JL et al (2020) Tau immunophenotypes in chronic traumatic encephalopathy recapitulate those of ageing and Alzheimer’s disease. Brain 143:1572–1587
pubmed: 32390044
pmcid: 7241956
doi: 10.1093/brain/awaa071
Schmidt M. Rey auditory verbal learning test: A handbook. Western Psychological Services Los Angeles, CA; 1996.
Lezak MD, Howieson DB, Loring DW, Fischer JS (2004) Neuropsychological assessment. Oxford University Press
Strauss E, Sherman EM, Spreen O (2006) A compendium of neuropsychological tests: administration, norms, and commentary. American Psychological Association
Wechsler D. WMS-III (1997) Wechsler memory scale administration and scoring manual. Psychological Corporation
Bench C, Frith C, Grasby P, Friston K, Paulesu E, Frackowiak R et al (1993) Investigations of the functional anatomy of attention using the Stroop test. Neuropsychologia 31:907–922
pubmed: 8232848
doi: 10.1016/0028-3932(93)90147-R
Smith A (1982) Symbol digit modalities test. Western Psychological Services Los Angeles
Nyhus E, Barceló F (2009) The Wisconsin Card Sorting Test and the cognitive assessment of prefrontal executive functions: a critical update. Brain Cogn 71:437–451
pubmed: 19375839
doi: 10.1016/j.bandc.2009.03.005
Kortte KB, Horner MD, Windham WK (2002) The trail making test, part B: cognitive flexibility or ability to maintain set? Appl Neuropsychol 9:106–109
pubmed: 12214820
doi: 10.1207/S15324826AN0902_5
Morey LC (1991) Personality assessment inventory. Psychological Assessment Resources Odessa
Geffen G, Moar K, O’hanlon A, Clark C, Geffen L (1990) Performance measures of 16–to 86-year-old males and females on the auditory verbal learning test. Clin Neuropsychol 4:45–63
pubmed: 29022439
doi: 10.1080/13854049008401496
Heaton R (1992) Comprehensive norms for an expanded Halstead-Reitan battery: a supplement for the Wechsler Adult Intelligence Scale-Revised. Psychological Assessment Resources, Odessa
Lewczuk P, Ermann N, Andreasson U, Schultheis C, Podhorna J, Spitzer P et al (2018) Plasma neurofilament light as a potential biomarker of neurodegeneration in Alzheimer’s disease. Alzheimer’s Res Ther Sprin 10:1–10
Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C et al (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33:341–355
pubmed: 11832223
doi: 10.1016/S0896-6273(02)00569-X
Taghdiri F, Chung J, Irwin S, Multani N, Tarazi A, Ebraheem A et al (2017) Decreased number of self-paced saccades in post-concussion syndrome associated with higher symptom burden and reduced white matter integrity. J Neurotrauma 35:719–729
doi: 10.1089/neu.2017.5274
Vasilevskaya A, Taghdiri F, Multani N, Anor C, Misquitta K, Houle S et al (2020) PET tau imaging and motor impairments differ between corticobasal syndrome and progressive supranuclear palsy with and without Alzheimer’s disease biomarkers. Front Neurol https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366127/
Rusjan P, Mamo D, Ginovart N, Hussey D, Vitcu I, Yasuno F et al (2006) An automated method for the extraction of regional data from PET images. Psychiatry Res 147:79–89
pubmed: 16797168
doi: 10.1016/j.pscychresns.2006.01.011
Müller-Gärtner HW, Links JM, Prince JL, Bryan RN, McVeigh E, Leal JP et al (1992) Measurement of radiotracer concentration in brain gray matter using positron emission tomography: MRI-based correction for partial volume effects. J Cereb Blood Flow Metab 12:571–583
pubmed: 1618936
doi: 10.1038/jcbfm.1992.81
Ossenkoppele R, Rabinovici GD, Smith R, Cho H, Schöll M, Strandberg O et al (2018) Discriminative accuracy of [18F] flortaucipir positron emission tomography for Alzheimer disease vs other neurodegenerative disorders. J Am Med Assoc 320:1151–1162
doi: 10.1001/jama.2018.12917
Fleisher AS, Pontecorvo MJ, Devous MD, Lu M, Arora AK, Truocchio SP et al (2020) Positron emission tomography imaging with [18F] flortaucipir and postmortem assessment of Alzheimer disease neuropathologic changes. JAMA Neurol Am Med Assoc 77:829–839
doi: 10.1001/jamaneurol.2020.0528
Goswami R, Dufort P, Tartaglia M, Green R, Crawley A, Tator C et al (2016) Frontotemporal correlates of impulsivity and machine learning in retired professional athletes with a history of multiple concussions. Brain Struct Function Spring 221:1911–1925
doi: 10.1007/s00429-015-1012-0
Dean PJ, Sato JR, Vieira G, McNamara A, Sterr A (2015) Long-term structural changes after mTBI and their relation to post-concussion symptoms. Brain Inj 29:1211–1218
pubmed: 26067623
doi: 10.3109/02699052.2015.1035334
Ware AL, Wilde EA, Newsome MR, Moretti P, Abildskov T, Vogt GS et al (2020) A preliminary investigation of corpus callosum subregion white matter vulnerability and relation to chronic outcome in boxers. Brain Imaging Behav 14:772–786
pubmed: 30565025
doi: 10.1007/s11682-018-0018-7
Wu Y-C, Harezlak J, Elsaid NMH, Lin Z, Wen Q, Mustafi SM et al (2020) Longitudinal white-matter abnormalities in sports-related concussion: a diffusion MRI study. Neurology 95:e781–e792 (Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology)
pubmed: 32641518
pmcid: 7605507
doi: 10.1212/WNL.0000000000009930
Asken BM, Tanner JA, VandeVrede L, Mantyh WG, Casaletto KB, Staffaroni AM, et al (2022) Plasma P-tau181 and P-tau217 in patients with traumatic encephalopathy syndrome with and without evidence of Alzheimer disease pathology. Neurology (AAN Enterprises)
Falcon B, Zivanov J, Zhang W, Murzin AG, Garringer HJ, Vidal R et al (2019) Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules. Nature 568:420
pubmed: 30894745
pmcid: 6472968
doi: 10.1038/s41586-019-1026-5
Benussi A, Karikari TK, Ashton N, Gazzina S, Premi E, Benussi L et al (2020) Diagnostic and prognostic value of serum NfL and p-Tau181 in frontotemporal lobar degeneration. J Neurol Neurosurg Psychiatry 91:960–967 (BMJ Publishing Group Ltd)
pubmed: 32611664
doi: 10.1136/jnnp-2020-323487
Ashton NJ, Hye A, Rajkumar AP, Leuzy A, Snowden S, Suárez-Calvet M et al (2020) An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders. Nat Rev Neurol 16:265–284
pubmed: 32322100
doi: 10.1038/s41582-020-0348-0
Gill J, Merchant-Borna K, Jeromin A, Livingston W, Bazarian J (2017) Acute plasma tau relates to prolonged return to play after concussion. Neurology 88:595–602 (Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology)
pubmed: 28062722
pmcid: 5304458
doi: 10.1212/WNL.0000000000003587