Abstract Details

Title Serum Neurofilament Light Associates with Microglial Activation in the Multiple Sclerosis Brain

Topic Multiple Sclerosis

Presentation(s) S26 - MS Imaging (2:48 PM-3:00 PM)

Poster/Presentation
Number 010

Background Innate immune cell activation is central for promoting neuroaxonal damage in MS and other neurodegenerative diseases. NfL on the other hand, is a biomarker released from damaged axons. TSPO-PET and NfL report on brain pathology, but their potential association has not yet been studied in MS in vivo.

Objective To evaluate the association between serum neurofilament light (NfL) and TSPO-PET-measurable microglial activation in the brain of clinically stable multiple sclerosis (MS) patients.

Design/Methods Microglial activation was detected using PET and the TSPO-binding radioligand [¹¹C]PK11195 in 44 MS patients (40 RRMS and 4 SPMS) and in 24 age and sex matched healthy controls (HC). Distribution volume ratio (DVR) was used to evaluate specific [¹¹C]PK11195-binding in brain. The 80^th percentile of the HC brain DVR was used as a cut-off value to define patients with unaltered or increased microglial activation. Serum levels of NfL were measured using single molecule array (Simoa).

Results

Nearly half of the patients (43%, n=19) had increased microglial activation in the brain compared to HC. These patients had higher EDSS and larger T1 hypo and T2 lesion volumes compared to patients with brain DVR values comparable to HC (p=0.047, p=0.019 and p=0.007, respectively). In the patient group with elevated brain DVR, serum NfL levels correlated with the DVR in thalamus [Spearman correlation coefficient (R)=0.60, p=0.006], T2 lesions (R=0.56, p=0.013), and perilesional normal appearing white matter (R=0.59, p=0.008). Moreover, NfL correlated positively with number and volume of TSPO-PET-detectable rim-active lesions defined by microglial activation at the plaque edge (i.e. smoldering lesions) and negatively with the proportion of inactive lesions. In patients with unaltered brain DVR no such associations were observed.

Conclusions Our demonstration of a strong association between TSPO-PET-measurable microglial activation and elevated serum NfL emphasizes the significance of smoldering inflammation for progression-promoting pathology in MS.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Marcus Sucksdorff, MD (University of Turku)	Dr. Sucksdorff has nothing to disclose.
David Leppert, MD (University Hospital Basel)	Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation for serving as an employee of GeNeuro. Dr. Leppert has received personal compensation for serving as an employee of Geneuro. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Leppert has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Leppert has received personal compensation in the range of $0-$499 for serving as a Consultant for Orion. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Dr. Leppert has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Quanterix. Dr. Leppert has stock in Novartis.
Jens Kuhle, MD	Dr. Kuhle has nothing to disclose.
Laura Airas, MD, PhD (Turku University Hospital)	The institution of Dr. Airas has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme. The institution of Dr. Airas has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis.