biostudies-literatureAlexander ANational Institute of Neurological Disorders and StrokeBLRD VAAndlinger FoundationBLRD Merit AwardVeterans Affairs BiorepositoryNational Institute of AgingWWENIA NIH HHSAlzheimer's AssociationNINDS NIH HHSConcussion Legacy FoundationBedford VA Healthcare SystemAlzheimer's AssociationU.S. Department of Veterans Affairs45https://www.ebi.ac.uk/biostudies/studies/S-EPMC11348287biostudies-literatureUnknown147(1)Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions (mean semiquantitative value ≤1) and classify them as cortical-sparing CTE (CSCTE). Of 620 brain donors with pathologically diagnosed CTE, 66 (11%) met criteria for CSCTE. ComparActa neuropathologicaCortical-sparing chronic traumatic encephalopathy (CSCTE): a distinct subtype of CTE.PMC11348287U01NS086659U54NS115266R01 NS122854K23NS102399NIRG-305779R01 AG075876I01BX005933U01 NS086659NIRG-362697RF1 NS122854RF1NS122854R01AG075876BX002466I01 BX005933RF1 NS132290I01 BX002466RF1 AG062348U54 NS115266K23 NS102399I01BX005161P30 AG072978I01 BX005161P30AG072978Mez JHuber BRGoldstein LEDwyer BAlvarez VEKowall NWStern RAMartin BStein TDPalmisano JMcKee ACAlosco MLDelalle ICantu RCTripodis YNicks RDaneshvar DHCrary JFAlexander ANowinski CKatz DIfalseCortical-sparing chronic traumatic encephalopathy (CSCTE): a distinct subtype of CTE.Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions (mean semiquantitative value ≤1) and classify them as cortical-sparing CTE (CSCTE). Of 620 brain donors with pathologically diagnosed CTE, 66 (11%) met criteria for CSCTE. Compar2024-01-01T00:00:00Z2024 Feb2026-06-03T04:40:31.825Z2025-04-04T00:21:37.181ZS-EPMC113482873840765110.1007/s00401-024-02690-5