Histological evidence of chronic traumatic encephalopathy in a large series of neurodegenerative diseases.

Abstract

population with or without NDDs which is currently not known. The most recent consecutive cases with the primary pathological diagnosis of PSP (N = 50), Parkinson’s disease (N = 50), AD (N = 20), corticobasal degeneration (CBD, N = 27), FTLD (N = 24) and multiple system atrophy (MSA, N = 50) and controls (>60 years old, N = 47) in the archives of the Queen Square Brain Bank for Neurological Disorders (QSBB) were included in this study. The QSBB brain donor programme is approved by a London Multi-Centre Research Ethics Committee and tissue is stored for research under a license from the Human Tissue Authority. Immunohistochemistry with antibodies to phosphorylated tau (AT8), Aβ, α-synuclein, TDP-43 was performed. Histological slides stained with the AT8 (frontal and temporal cortices, hippocampal formation, midbrain, pons and medulla) and Aβ antibodies (frontal cortex and hippocampal formation) were reviewed by one neuropathologist (TR). Cases considered to have positive CTE histology were then reviewed by a second neuropathologist (JH) and a consensus was achieved by a joint review of the cases. The interpretation of CTE histological changes can be challenging in co-existing tauopathies. A case is determined to have positive CTE pathology when the following distinctive features are present [11]: (1) perivascular foci of taupositive lesions in the neurons, astrocytes and neurites in the neocortex; (2) irregular distribution of these tau-positive lesions at the sulcal depths; (3) clusters of subpial ATs. The medical records of the positive cases were reviewed; family members were interviewed by a QSBB research nurse to screen for past history and risk factors for TBIs. Of the 268 screened NDDs and control cases, 32 cases (11.9 %, M:F = 19:13) had histological evidence of CTE (Table 1). The prevalence of CTE was highest in PSP Chronic traumatic encephalopathy (CTE) is a long-term neurodegenerative consequence of repetitive traumatic brain injury (rTBI). The histological features of CTE are characterised by neurofibrillary tangles (NFTs) composed of both 3-repeat and 4-repeat tau isoforms and astrocytic tau pathology (ATs) commonly in the frontal and temporal cortices and are distinct from other tauopathies [9]. The recent classification delineates 4 pathological stages with progression of tau pathology from multifocal (I and II) to widespread disease (III and IV) [12]. Of 68 CTE cases in the McKee series with history of rTBIs, only 43 had pure CTE pathology, the other 25 cases (37 %) had co-morbid neurodegenerative disorders (NDDs) including Lewy body disease, motor neuron disease, Alzheimer’s disease (AD), frontotemporal lobar degeneration (FTLD), Pick’s disease and progressive supranuclear palsy (PSP) [12]. TDP43 pathology was found in 85 % of CTE cases across all disease stages [12]. Our group reported an ex-professional boxer with dual pathologies of CTE and PSP [10]. It is possible that rTBIs or the existence of chronic CTE-tau pathology play a role in triggering the deposition of other abnormal proteins in the brain [17, 18]. The existing literature mainly focused on high-risk individuals especially contact sport athletes. This study aimed to investigate the prevalence of histological evidence of CTE in the general