Microglial activation correlates with disease progression and upper motor neuron clinical symptoms in amyotrophic lateral sclerosis.
OBJECTIVE
We evaluated clinicopathological correlates of upper motor neuron (UMN) damage in amyotrophic lateral sclerosis (ALS), and analyzed if the presence of the C9ORF72 repeat expansion was associated with alterations in microglial inflammatory activity.


METHODS
Microglial pathology was assessed by IHC with 2 different antibodies (CD68, Iba1), myelin loss by Kluver-Barrera staining and myelin basic protein (MBP) IHC, and axonal loss by neurofilament protein (TA51) IHC, performed on 59 autopsy cases of ALS including 9 cases with C9ORF72 repeat expansion.


RESULTS
Microglial pathology as depicted by CD68 and Iba1 was significantly more extensive in the corticospinal tract (CST) of ALS cases with a rapid progression of disease. Cases with C9ORF72 repeat expansion showed more extensive microglial pathology in the medulla and motor cortex which persisted after adjusting for disease duration in a logistic regression model. Higher scores on the clinical UMN scale correlated with increasing microglial pathology in the cervical CST. TDP-43 pathology was more extensive in the motor cortex of cases with rapid progression of disease.


CONCLUSIONS
This study demonstrates that microglial pathology in the CST of ALS correlates with disease progression and is linked to severity of UMN deficits.
Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America. Johannes.brettschneider@uni-ulm.de
Johannes
J
Brettschneider
Jon B
JB
Toledo
Vivianna M
VM
Van Deerlin
Lauren
L
Elman
Leo
L
McCluskey
Virginia M-Y
VM
Lee
John Q
JQ
Trojanowski
D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D001369:Axons; D001483:Base Sequence; D015331:Cohort Studies; D017931:DNA Primers; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D017628:Microglia / Q000473:pathology*; D008875:Middle Aged; D009046:Motor Neurons / Q000473:pathology*; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction
D017931:DNA Primers