Abstract Details

Title TDP-43 Inclusions in the Spinal Cord: Sensitivity and Specificity for the Diagnosis of Sporadic ALS

Topic Anterior Horn

Presentation(s) P02 - (-)

Poster/Presentation
Number 171

Objective

Background BACKGROUND: TDP-43 inclusions are frequently found in the spinal cords of patients with ALS, as well as in the brains of patients with dementing illnesses who do not have evidence of motor neuron disease. To determine the sensitivity and specificity of TDP-43 inclusions in the spinal cord for the diagnosis of ALS, we compared patients with ALS to those with Alzheimer's disease (AD) and other dementing illnesses.

Design/Methods DESIGN/METHODS: Brainstem and spinal cord sections from 81 autopsy cases were analyzed. 27 had a clinical diagnosis of ALS, 1 with an SOD-1 mutation. 39 had AD and 3 had FTLD-U. The remainder had the following: 3 DLB, 2 PSP, 2 tauopathy, 1 NIFID, 1 with non-specific changes, and 3 infarcts. Sections were systematically analyzed for the presence of glial and neuronal TDP-43 inclusions.

Results RESULTS: TDP-43 neuronal or glial inclusions were found in all 26 cases of sporadic ALS, but not in the case of SOD-1 related ALS. 25 of the 26 sporadic cases had neuronal inclusions, and 1 had only glial inclusions. TDP-43 inclusions were also found in 4/39 of the AD cases and 2/3 of the FTLD-U cases, but not in cases with any other diagnosis. The sensitivity and specificity for the diagnosis of sporadic ALS was as follows: all inclusions - sensitivity 100%, specificity 90.9%; neuronal inclusions - sensitivity 96%, specificity 96%; glial inclusions - sensitivity 81%, specificity 95%.

Conclusions CONCLUSIONS: These findings demonstrate that a clinical diagnosis of ALS strongly predicts the presence of TDP-43 inclusions in the spinal cord. This finding should be considered a neuropathologic diagnostic feature of ALS. However, some cases without a clinical diagnosis of ALS can show TDP-43 immunoreactivity in the spinal cord.

Authors/Disclosures
Saila Upadhyayula, MD (Emory University) PRESENTER	Dr. Upadhyayula has nothing to disclose.
	No disclosure on file
Jonathan D. Glass, MD (Emory University School of Medicine)	Dr. Glass has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Glass has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Apic Bio. Dr. Glass has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CIRM. Dr. Glass has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Bryan Cave Leighton Paisner. The institution of Dr. Glass has received research support from NIH. The institution of Dr. Glass has received research support from ALS Assoiciation. The institution of Dr. Glass has received research support from Muscular Dystrophy Assoication.
Michael N. Diringer, MD (Washington Univ/Dept Neurology)	No disclosure on file

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