Abstract Details

Title Greater Relative White Matter Burden is a Distinct Feature of Tauopathies in Frontotemporal Degeneration Spectrum

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-006

Objective To objectively quantify neuropathological white matter (WM) burden in relation to grey matter (GM) in frontotemporal lobar degeneration (FTLD) subtypes.

Background Antemortem distinction of FTLD proteinopathies, including tauopathies (FTLD-Tau) and TDP-43 proteinopathies (FTLD-TDP), is critical for disease-modifying therapies. Pathological heterogeneity in patterns of GM and WM pathology across FTLD subtypes is understudied. Shared neuropathological features of proteinopathies could facilitate antemortem diagnostic tools.

Design/Methods We studied neuropathological burden in five cortical GM and adjacent WM regions in an autopsy cohort of FTLD (n=92) using a novel, validated digital image approach. Using linear mixed-effects models we examined absolute density of WM pathology and relative WM burden (i.e. WM-to-GM ratio) across FTLD subtypes (FTLD-TDP: type A/B/E=42 patients vs. type C=13; FTLD-Tau: progressive supranuclear palsy [PSP]=9, corticobasal degeneration [CBD]=11, Pick’s disease [PiD]=11, MAPT-mutation carriers=6).

Results A positive linear association between absolute GM and WM burden was found in both FTLD-Tau (p<0.001) and FTLD-TDP (p<0.001). In FTLD-Tau, CBD had greater absolute WM burden than PSP (p<0.001) and PiD (p<0.001). In FTLD-TDP, type A/B/E had greater absolute WM burden than type C (p<0.001). Relative WM burden was greater in FTLD-Tau overall than FTLD-TDP (p<0.001). Of FTLD-Tau subtypes, CBD, PSP and PiD all had greater relative WM burden than FTLD-TDP (p≤0.001). Compared to FTLD-TDP subtypes, CBD and PSP had higher relative WM burden than FTLD-TDP type C (p<0.001) as well as type A/B/E (p<0.013), while PiD and MAPT-mutation carriers had higher relative WM burden than FTLD-TDP type C (p<0.001). WM pathology showed region-specific patterns in both proteinopathies (p<0.001), with greatest relative WM burden in superior temporal gyrus in FTLD-Tau and in mid-frontal cortex in FTLD-TDP.

Conclusions FTLD-Tau subgroups share the distinctive feature of greater relative WM pathology differing from FTLD-TDP. These findings suggest that in vivo WM biomarkers may have diagnostic value for molecular pathology in clinical forms of FTLD.

Authors/Disclosures
Lucia Giannini PRESENTER	No disclosure on file
Corey McMillan, PhD (University of Pennsylvania)	Dr. McMillan has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. McMillan has received research support from Biogen. The institution of Dr. McMillan has received research support from NIH.
	No disclosure on file
David A. Wolk, MD, FAAN (University of Pennsylvania)	Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Functional Neuromodulation. Dr. Wolk has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for GSK. The institution of Dr. Wolk has received research support from Biogen. Dr. Wolk has received publishing royalties from a publication relating to health care. Dr. Wolk has received personal compensation in the range of $5,000-$9,999 for serving as a CME speaker with Eli Lilly.
	No disclosure on file
John Q. Trojanowski, MD, PhD (University of PA School of Med)	Dr. Trojanowski has nothing to disclose.
Murray Grossman, MD, FAAN (University of Pennsylvania)	Dr. Grossman has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Neurology. The institution of Dr. Grossman has received research support from NIH.
David Irwin, MD (University of Pennsylvania)	The institution of Dr. Irwin has received research support from NIH. The institution of Dr. Irwin has received research support from Prevail. The institution of Dr. Irwin has received research support from Passage Bio. The institution of Dr. Irwin has received research support from Alector. The institution of Dr. Irwin has received research support from Transposon. The institution of Dr. Irwin has received research support from Denali. The institution of Dr. Irwin has received research support from Cervo Med.

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