Prevalence of chronic traumatic encephalopathy in the Sydney Brain Bank

Abstract

Chronic traumatic encephalopathy neuropathologic change can only be definitively diagnosed post-mortem. It has been associated with repetitive mild neurotrauma sustained in amateur and professional contact, collision and combat sports, although it has also been documented in people with a single severe traumatic brain injury and in some people with no known history of brain injury. The characteristic neuropathology is an accumulation of perivascular neuronal and astrocytic phosphorylated tau in the depths of the cortical sulci. The tau-immunopositive neurons and astrocytes that are considered pathognomonic for chronic traumatic encephalopathy are morphologically indistinguishable from Alzheimer-related neurofibrillary tangles and ageing-related tau astrogliopathy, respectively, although they are found in different spatial distributions throughout the cortex. The Sydney Brain Bank collection consists of neurodegenerative diseases and neurologically normal controls. We screened 636 of these cases for chronic traumatic encephalopathy neuropathologic change. A subset of 109 cases had a known history of traumatic brain injury. Three cortical regions were screened for the presence of neuronal and astrocytic phosphorylated tau according to the current 2021 National Institute on Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering consensus criteria for chronic traumatic encephalopathy. Five cases (0.79%) showed pathological evidence of chronic traumatic encephalopathy and three of these had a history of traumatic brain injury. Three cases had coexisting Alzheimer's and/or Lewy body disease pathology meeting criteria for neurodegenerative disease. Another eight cases almost met criteria for chronic traumatic encephalopathy neuropathological change except for an absence of neuronal tau or a strict perivascular arrangement. Ageing-related tau astrogliopathy was found in all eight cases as a coexisting neuropathology. Traumatic brain injury was associated with increased odds ratio [1.79, confidence interval 1.18-2.72] of having a higher neurofibrillary tangle stage and phosphorylated TAR DNA binding protein 43 (OR 2.48, confidence interval 1.35-4.54). Our study shows a very low rate of chronic traumatic encephalopathy neuropathological change in brains with or without neurodegenerative disease from the Sydney Brain Bank. Our evidence suggests that isolated traumatic brain injury in the general population is unlikely to cause chronic traumatic encephalopathy neuropathologic change but may be associated with increased brain ageing.

Keywords: chronic traumatic encephalopathy; phosphorylated tau; traumatic brain injury.

Graphical Abstract

Figure 1

Representative images of definite and almost CTE-NC. (A–E) CTE-NC in cases with definite tau-immunopositive neuronal and astrocytic perivascular lesions at the depth of the sulcus. Black boxes indicate the location of the high magnification image on the right (F–J). Black arrow on A indicates pial surface of sulcus. (K–O) Representative images of five of the eight cases that almost met criteria for CTE-NC, except for a lack of either a perivascular distribution (K, L, M, O) and/or lack of a tau-immunopositive neuronal component (K, N, O). Black boxes indicate the location of the high magnification image on the right (P–T). B, C, D, K, M, N, O, middle frontal gyrus; A, superior/middle temporal gyrus; E and L, inferior parietal gyrus. Scale bars A–E = 200 µm; F–J = 50 µm.

Figure 2

Box plots illustrating the association between TBI and B score and TDP-43 probability. A multivariate ordinal regression model with multivariate logit link was used to assess associations between pathological features of common neurodegenerative diseases and TBI, age (mean centred average), gender, and post-mortem delay (N = 507). Although TBI history was not associated with A score (amyloid), Braak Lewy body score or presence of ARTAG, both (A) neurofibrillary tangles (B score, P = 0.006) and (B) TDP-43 aggregation (LATE P = 0.003) increased significantly in these cases. The x- axis in (A) shows the four neurofibrillary tangle Stages 0–III and in (B) whether LATE was present or absent. The y-axis in both plots shows the change in predicted probability for a given outcome due to head injury. The number of data points analysed for each group for B score 0 = 117, 1 = 117, 2 = 159, 3 = 114; LATE yes = 332, no = 175.