Neuropathology in Chronic Traumatic Encephalopathy (CTE)
with Motor Neuron Disease Compared to CTE and ALS
Trever Symalla BS, Thor Stein MD/PhD, Christopher Leung MS, Lauren Ferrerosa MS, Anne McKee MD, Center for the Study of
Traumatic Encephalopathy, Boston University School of Medicine
Background
Tau Scoring Scale
Score
Number of NFT’s *
(20X field)
Number of NFT’s
(Amygdala/
Hippocampus)
0
0
0
1
1
1-9
2
2-5
10-19
3
6-9
20-29
4
10+
30+
0.80
CTE
CTEM
0.60
0.40
0.20
0.00
* Sample Size: 9
CTEM cases, 16 CTE
cases, matched for
stage of CTE
TDP-43 Positive Cases
1.00
ALS in Athletes: It has been shown that there is a
significant increased incidence of ALS within athletes,
especially professional football players. A recent study
showed that there was a 4 times increased mortality from
ALS and AD in professional football players.
Stage 1
Stage 2
0.80
0.60
0.40
CTEM
0.20
0.00
Substantia Nucleus of Motor Anterior
Nigra
12
Nucleus of Horn
10
CTE with Motor Neuron Disease (CTEM) is a subset of CTE
patients that also meet the diagnosis of ALS. Normally, CTE
doesn’t present with motor neuron disease but there are a
significant number of individuals that have been diagnosed
with CTE that also have motor neuron dysfunction. When
looking at the gross pathology, these individuals show similar
changes to those in ALS, particularly degeneration of the
lateral cortical spinal tracts and loss of alpha motor neurons
in anterior horn cells.
Examine the distribution of tau and TDP-43
in CTEM and compare it to the distribution
of tau in CTE and the distribution of TDP-43
in ALS.
1.00
* NFT: Neurofibrillary Tangles
Amyotrophic Lateral Sclerosis (ALS) is a
neurodegenerative disease that is characterized by the loss of
both upper and lower motor neuron function. ALS can be
sporadic or have a genetic cause. While a variety of protein
inclusions have been found in ALS, the most prevalent are
TDP-43 inclusions.
Objective
Tau Positive Cases
Percentage of Cases
CTE Pathology is characterized by neurofibrillary tangles
containing phosphorylated tau that accumulates in a
characteristic pattern that is unique to CTE. The tau is found
first in the depths of the sulci and perivascularly. The tau
pattern is distinct from Alzheimer's disease (AD) and amyloid
plaques are not present in CTE. Pathology that is more
characteristic of other diseases has also been seen in subsets
of individuals that have been diagnosed with CTE. These
include TDP-43 inclusions seen in frontal temporal dementia
(FTD) and ALS as well as Lewy bodies that are seen in Lewy
body dementia and Parkinson’s disease.
Scoring Method: Each brain is preserved and
sectioned by specific brain regions. The slides
where stained using immunohistochemistry for
either phosphorylated tau or TDP-43. Each slide
was examined using a light microscope in a 20X
field and scored based on the scales below.
Percentage of Cases
Chronic Traumatic Encephalopathy (CTE) is a
neurodegenerative disease that is caused by mild repetitive
head trauma. This trauma is commonly seen in contact
sports, such as football and boxing. CTE has also developed
in military members exposed to blasts and autistic children
who repetitively bang their heads on a wall. Clinically, CTE
presents with memory difficulties, loss of concentration,
mood changes that include aggression and erratic behavior,
and suicidal thoughts and actions.
Results
Methods
Conclusions
Stage 3
Stage 4
TDP-43 Scoring Scale
Score
Number of Inclusions
0
0
1
1-2, or neurites
2
2-3
3
4-9
4
10+
The data clearly illustrates that, in the area’s selected, the tau pathology
in CTE and CTEM are the same. This indicates that the disease process
leading to the clinical picture of CTE in both CTE and CTEM demonstrates
the same pathological processes. The next step is to obtain the TDP-43
profile for ALS cases and compare it to CTEM. If they align in the same
matter, then it will appear that the same process was involved in each. If
the pathologies differ, that would suggest that there is a link between the
CTE and motor changes.
References
McKee AC, Gavett, BE, Stern RA,, Nowinski CJ,, Cantu RC, Kowall NW., Perl DP, Hedley-Whyte ET,
Price B, Sullivan C, Morin P, Lee H, Kubilus CA, Daneshvar DH, Wulff M, Budson AE. (2010) J
Neuropathol Exp Neurol 69(9), 918-29. Lehman EJ, Hein MJ, Baron SL, Gersic CM. (2012) Neurology
79, 1-5.