Pathology Research

The pathological research department at the BU CTE Center, operates the UNITE Brain Bank and BU ADRC Brain Bank, and works closely with the Framingham Heart Study (FHS) Brain Bank and Department of Veterans Affairs Biorepository Brain Bank (VABBB) to study tissue and fluid samples from brain donors. Our neuropathologists examine frozen and fixed tissue for genetic, molecular, and other projects, and to provide UNITE and BU ADRC brain donor families with diagnoses. They work to publicize the findings and maintain the storage of the tissue and samples.

UNITE Brain Bank

The UNITE Brain Bank is the largest tissue repository in the world focused on traumatic brain injuries (TBI) and chronic traumatic encephalopathy (CTE). The brain bank collects central nervous system tissue samples (brain, spinal cord and eyes) from deceased athletes, military veterans, and others to better understand the long-term effects of repetitive head impacts, TBI and CTE. Ann McKee, MD and her team of neuropathologists, clinicians, and investigators have published more than 175 peer-reviewed papers and studies focused on CTE in highly regarded journals. They’ve also written more than 30 grants to support the daily operations of the brain bank.

Team

Pathology Images

Source: Structural MRI profiles and tau correlates of atrophy in autopsy-confirmed CTE

Figure 4. MRI and autopsy patterns of atrophy and P-tau deposition in a brain donor with CTE

The figure shows an antemortem axial (A) and coronal (D) T1 MRI sequence and corresponding gross atrophy at autopsy (B, C, E) of a male former professional American football player with CTE stage IV. The antemortem MRI scan was done when he was in his early 60’s and he died in his mid-70s and donated his brain. The antemortem MRI and neuropathological examination both showed frontal and temporal cortical atrophy (A–E) along with atrophy of medial temporal lobe structures (C, E) including the hippocampus and amygdala.

Source: Association Between Antemortem FLAIR White Matter Hyperintensities and Neuropathology in Brain Donors Exposed to Repetitive Head Impacts

Figure 1. Example of FLAIR and Lesion Segmentation From the Lesion Prediction Algorithm of the Lesion Segmentation Toolbox 

Fluid-attenuated inversion recovery (FLAIR) scan of a mid-70-year-old former professional American football player with autopsy-confirmed stage III/IV chronic traumatic encephalopathy. White matter hyperintensities were quantified using log-transformed values for the total lesion volume, calculated using the lesion prediction algorithm (LPA) from the Lesion Segmentation Toolbox. The LPA segments lesions in new images by providing an estimate for the lesion probability for each voxel. Total lesion volume in milliliters is extracted by thresholding derived lesion probability maps at a threshold kappa of 0.5 (default LPA recommendation) and only lesions with volume >0.015 mL are counted. The top row (A) contains the native FLAIR sequence and the bottom row (B) contains the corresponding lesion belief maps overlaid on the FLAIR with lesion threshold at 0.5 using Slicer.

Source: TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy 

FIGURE 2 

Spinal cord pathology in chronic traumatic encephalopathy (CTE) with TAR DNA-binding protein of approximately 43 kd (TDP-43) proteinopathy, tauopathy, and motor neuron disease (CTE + MND). (A, B) Whole-mount 50-μm sections of lumbar and thoracic spinal cord immunostained with antibody AT8 showing abundant tau immunostaining in the ventral horns. (C) Tau-positive astrocytic tangles in the ventral horn of Case 1 (AT8 immunostain, original magnification: 100×). (D) Whole-mount 10-μm section through high thoracic spinal cord showing marked myelin and axonal loss in the lateral and ventral corticospinal tracts. Atrophic ventral roots are not visible. Luxol fast blue hematoxylin and eosin stain, original magnification: 1×. (E) Whole-mount 50-μm section of high thoracic cord showing intense immunoreactivity for activated microglia and macrophages in lateral and corticospinal tracts (LN-3 immunostain, original magnification: 1×). (F) Tau-positive neurofibrillary tangles in ventral horn of Case 3, AT8 immunostain, original magnification: 600×. (G) TDP-43 immunoreactivity in ventral horn, original magnification: 50×. (H) TDP-43 immunoreactive filamentous neuronal inclusions (FNIs), ring-shaped glial inclusions (RGIs), and ring-shaped neurites (RNs) in the ventral horns of the lumbar spinal cord in Case 3, original magnification: 200×. (I) Tau-positive astrocytes and their processes surrounding degenerating anterior horn cells in the thoracic spinal cord (AT8 immunostain, original magnification: 350×). (J) TDP-43–positive FNIs, RGIs, and RNs in the ventral horns of the lumbar spinal cord in Case 2, original magnification: 200×. (K) TDP-43–positive FNI in the anterior horn, original magnification: 400×.(L) Double immunostained sections show tau-positive astrocytes (brown) and their processes surrounding anterior horn neurons containing TDP-43–positive filamentous inclusions (red), PHF-1 and TDP-43 immunostains, original magnification: 400×. (M) TDP-43–positive FNIs, RGIs, and RNs in the lumbar ventral horns in Case 1, original magnification: 200×. (N) TDP-43–positive FNIs in the anterior horn, original magnification: 400×. (O) Double immunostained sections showing tau-positive astrocytes (brown) and their processes surrounding anterior horn neurons containing TDP-43–positive FNIs (red), PHF-1 and TDP-43 immunostains, original magnification: 600×.

To request access to biological samples from the UNITE Brain Bank, please review our data request process.