Abstract Details

Title DTI Abnormalities in Healthy E200K Carriers May Serve as an Early Biomarker for Genetic Creuzfeldt-Jakob Disease (gCJD)

Topic General Neurology

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 168

Objective To investigate microstructural changes in healthy E200K carriers using diffusion tensor imaging (DTI).

Background Creuzfeldt-Jakob disease (CJD) is the most common prion disease in humans, leading an aggressive course and death within months. Genetic CJD (gCJD) is caused by mutations on the PRNP gene. While the mutation is inborn, symptoms usually appear in late adulthood. MRI plays an important role the disease diagnosis, however its role in the prodromal phase remains unclear.

Design/Methods

Seven symptomatic gCJD patients and N=60 healthy relatives of gCJD patients were included. Participants underwent genetic testing for the E200K mutation, MRI scans at 3T, and a lumbar puncture (LP) for total Tau protein levels (t-Tau). Diffusion tensor imaging (DTI) metrics including; fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axonal diffusivity (AD) were calculated along 45 WM tracts.

Results N=30 participants were found to be E200K carriers (mean age 56.73±7.27, 18F). Of those; N=23 underwent an LP, and 8 showed above normal t-Tau values (> 290 pg/ml). Higher MD, RD as well as lower FA and AD values were observed in symptomatic CJD patients compared to healthy relatives in several WM tracts (Two-samples t-test; p<0.05). Non-carriers demonstrated higher FA in the right anterior and posterior limbs of internal capsule compared to carriers (Two-samples t-test; p<0.05). Finally, significantly higher FA and lower MD, RD, and AD were found in carriers with high level of t-Tau compared to carriers with normal levels of t-Tau along several WM tracts.

Conclusions

DTI abnormalities along WM tracts were found in healthy E200K carriers with elevated t-Tau in CSF. These findings suggest a possible role for DTI imaging as a non-invasive biomarker for prodromal gCJD. Ongoing work is focused on identifying DTI measures and additional candidate MRI markers prior to phenoconversion.

Authors/Disclosures
PRESENTER	No disclosure on file
Rawan Silbak	Miss Silbak has nothing to disclose.
	No disclosure on file
Tamara Shiner	Tamara Shiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli lilly. Tamara Shiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Tamara Shiner has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Tamara Shiner has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. The institution of Tamara Shiner has received research support from MJFF.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Nir Giladi, MD, FAAN (Tel-Aviv Medical Center)	Dr. Giladi has received personal compensation in the range of $0-$499 for serving as a Consultant for Sionara. Dr. Giladi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NeuroDerm. Dr. Giladi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pharma2B. Dr. Giladi has stock in Vibrant. Dr. Giladi has stock in Lysosomal Therapeutics . The institution of Dr. Giladi has received research support from The Michael J Fox Foundation. The institution of Dr. Giladi has received research support from The National Parkinson Foundation. The institution of Dr. Giladi has received research support from The European Union . The institution of Dr. Giladi has received research support from The Israel Science Foundation. The institution of Dr. Giladi has received research support from Biogen . The institution of Dr. Giladi has received research support from Ionis. The institution of Dr. Giladi has received research support from Sieratzki Family Foundation . The institution of Dr. Giladi has received research support from The Aufzien Academic Center in Tel-Aviv University.
	No disclosure on file
Noa Bregman	Noa Bregman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Medison. The institution of Noa Bregman has received research support from Ionis pharmaceuticals.

��ɫ��

��ɫ��