TY - JOUR
T1 - Contact sport participation and chronic traumatic encephalopathy are associated with altered severity and distribution of cerebral amyloid angiopathy
AU - Standring, Oliver J.
AU - Friedberg, Jacob
AU - Tripodis, Yorghos
AU - Chua, Alicia S.
AU - Cherry, Jonathan D.
AU - Alvarez, Victor E.
AU - Huber, Bertrand R.
AU - Xia, Weiming
AU - Mez, Jesse
AU - Alosco, Michael L.
AU - Nicks, Raymond
AU - Mahar, Ian
AU - Pothast, Morgan J.
AU - Gardner, Hannah M.
AU - Meng, Gaoyuan
AU - Palmisano, Joseph N.
AU - Martin, Brett M.
AU - Dwyer, Brigid
AU - Kowall, Neil W.
AU - Cantu, Robert C.
AU - Goldstein, Lee E.
AU - Katz, Douglas I.
AU - Stern, Robert A.
AU - McKee, Ann C.
AU - Stein, Thor D.
N1 - Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Cerebral amyloid angiopathy (CAA) consists of beta-amyloid deposition in the walls of the cerebrovasculature and is commonly associated with Alzheimer’s disease (AD). However, the association of CAA with repetitive head impacts (RHI) and with chronic traumatic encephalopathy (CTE) is unknown. We evaluated the relationship between RHI from contact sport participation, CTE, and CAA within a group of deceased contact sport athletes (n = 357), a community-based cohort (n = 209), and an AD cohort from Boston University AD Center (n = 241). Unsupervised hierarchal cluster analysis demonstrated a unique cluster (n = 11) with increased CAA in the leptomeningeal vessels compared to the intracortical vessels (p < 0.001) comprised of participants with significantly greater frequencies of CTE (7/11) and history of RHI. Overall, participants with CTE (n = 251) had more prevalent (p < 0.001) and severe (p = 0.010) CAA within the frontal leptomeningeal vessels compared to intracortical vessels. Compared to those with AD, participants with CTE had more severe CAA in frontal than parietal lobes (p < 0.001) and more severe CAA in leptomeningeal than intracortical vessels (p = 0.002). The overall frequency of CAA in participants with CTE was low, and there was no significant association between contact sport participation and the presence of CAA. However, in those with CAA, a history of contact sports was associated with increased CAA severity in the frontal leptomeningeal vessels (OR = 4.01, 95% CI 2.52–6.38, p < 0.001) adjusting for AD, APOE ε4 status, and age. Participants with CAA had increased levels of sulcal tau pathology and decreased levels of the synaptic marker PSD-95 (p’s < 0.05), and CAA was a predictor of dementia (OR = 1.75, 95% CI 1.02–2.99, p = 0.043) adjusting for age, sex, and comorbid pathology. Overall, contact sport participation and CTE were associated with more severe frontal and leptomeningeal CAA, and CAA was independently associated with worse pathological and clinical outcomes.
AB - Cerebral amyloid angiopathy (CAA) consists of beta-amyloid deposition in the walls of the cerebrovasculature and is commonly associated with Alzheimer’s disease (AD). However, the association of CAA with repetitive head impacts (RHI) and with chronic traumatic encephalopathy (CTE) is unknown. We evaluated the relationship between RHI from contact sport participation, CTE, and CAA within a group of deceased contact sport athletes (n = 357), a community-based cohort (n = 209), and an AD cohort from Boston University AD Center (n = 241). Unsupervised hierarchal cluster analysis demonstrated a unique cluster (n = 11) with increased CAA in the leptomeningeal vessels compared to the intracortical vessels (p < 0.001) comprised of participants with significantly greater frequencies of CTE (7/11) and history of RHI. Overall, participants with CTE (n = 251) had more prevalent (p < 0.001) and severe (p = 0.010) CAA within the frontal leptomeningeal vessels compared to intracortical vessels. Compared to those with AD, participants with CTE had more severe CAA in frontal than parietal lobes (p < 0.001) and more severe CAA in leptomeningeal than intracortical vessels (p = 0.002). The overall frequency of CAA in participants with CTE was low, and there was no significant association between contact sport participation and the presence of CAA. However, in those with CAA, a history of contact sports was associated with increased CAA severity in the frontal leptomeningeal vessels (OR = 4.01, 95% CI 2.52–6.38, p < 0.001) adjusting for AD, APOE ε4 status, and age. Participants with CAA had increased levels of sulcal tau pathology and decreased levels of the synaptic marker PSD-95 (p’s < 0.05), and CAA was a predictor of dementia (OR = 1.75, 95% CI 1.02–2.99, p = 0.043) adjusting for age, sex, and comorbid pathology. Overall, contact sport participation and CTE were associated with more severe frontal and leptomeningeal CAA, and CAA was independently associated with worse pathological and clinical outcomes.
KW - Alzheimer’s disease
KW - American football
KW - Cerebral amyloid angiopathy
KW - Chronic traumatic encephalopathy
KW - Mild traumatic brain injury
KW - Repetitive head impacts
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U2 - 10.1007/s00401-019-02031-x
DO - 10.1007/s00401-019-02031-x
M3 - Article
C2 - 31183671
AN - SCOPUS:85067280043
SN - 0001-6322
VL - 138
SP - 401
EP - 413
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 3
ER -