Abstract Details

Title Neuroinflammation biomarker in non-fluent/agrammatic variant of primary progressive aphasia and/or apraxia of speech

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-002

Background

Neuroinflammation, a hallmark of frontotemporal dementia and a potential therapeutic target, has been sparsely studied in vivo. We used ¹¹C-PBR28 PET to measure TSPO levels in patients with nfvPPA) and/or AOS.

Objective

To determine the anatomic specificity of translocator protein 18 kDa (TSPO) imaging in non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and/or apraxia of speech (AOS).

Design/Methods

Sixteen patients (9/16 women, age 65±5.9 years) with nfvPPP/AOS underwent PET using ¹¹C-PBR28 and ¹⁸F-flortaucipir. Patients were PET amyloid-negative except two, with a non-AD flortaucipir PET. Thirty healthy controls (17/30 women, age 66±9.3 years) underwent PET imaging using ¹¹C-PBR28 (13 controls) or ¹⁸F-flortaucipir (17 controls). V_T values for ¹¹C-PBR28 were calculated with the Logan plot and a metabolite-corrected arterial input function. For ¹⁸F-flortaucipir, the SUV ratio over the cerebellar gray matter was calculated for t = 80-100 min. A full factorial analysis was performed on V_T and SUVR values.

Results

Compared to controls, patients had increased V_T and SUVR values (p < 0.001 uncorrected) in left inferior, middle and superior frontal gyri, as well as in the left putamen and pallidum. However, peak uptake of ¹⁸F-flortaucipir was localized in Broca’s area, epicenter of the pathology, while the distribution of ¹¹C-PBR28 V_T was more extensive in the frontal lobe, including precentral gyrus, and other regions outside of the frontal lobe, as the supramarginal gyrus and superior temporal sulcus, as well as a small area in the posterior extent of the right inferior frontal gyrus.

Conclusions

¹¹C-PBR28 and ¹⁸F-flortaucipir uptake patterns corresponded to anatomical areas known to be involved in nfvPPA and apraxia of speech. Thus, ¹¹C-PBR28 seems to be a suitable radioligand for detecting neuroinflammation in nfvPPA. Furthermore, the more extensive anatomical distribution of abnormal ¹¹C-PBR28 uptake, as compared to ¹⁸F-flortaucipir uptake, suggests that inflammation is key to the progression of the pathologic process in nfvPPA.

Authors/Disclosures
Belen Pascual, PhD (Houston Methodist Hospital) PRESENTER	The institution of Prof. Pascual has received research support from NIH. The institution of Prof. Pascual has received research support from NIH.
Quentin Funk	No disclosure on file
Kathleen Bradbury (Houston Methodist Hospital)	Ms. Bradbury has nothing to disclose.
Johanna Appleton (Houston Methodist)	No disclosure on file
Paolo Zanotti Fregonara	Paolo Zanotti Fregonara has nothing to disclose.
Mohammad O. Nakawah, MD, FAAN (Houston Methodist Hospital)	Dr. Nakawah has nothing to disclose.
David R. Beers, PhD (Houston Methodist Neurological Institute)	No disclosure on file
Alirexa Faridar, MD (Methodist Neurological Institute)	Dr. Faridar has nothing to disclose.
Stanley H. Appel, MD, FAAN (Methodist Neurological Institute)	Dr. Appel has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Appel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eledon. The institution of Dr. Appel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Implicit. The institution of Dr. Appel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Coya Therapeutics. Dr. Appel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Muscular Disease Association. Dr. Appel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ALS Therapy Development Institute. Dr. Appel has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for ALS Finding a Cure. Dr. Appel has stock in Stock holdings in retirement acct at Fidelity. The institution of Dr. Appel has received research support from Coya Therapeutics.
	No disclosure on file
Joseph C. Masdeu, MD, PhD, FAAN (Houston Methodist Neurological Institute)	Dr. Masdeu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Masdeu has received research support from NIH. The institution of Dr. Masdeu has received research support from Moody Foundation. The institution of Dr. Masdeu has received research support from Biogen. The institution of Dr. Masdeu has received research support from Eli Lilly. The institution of Dr. Masdeu has received research support from Eisai. The institution of Dr. Masdeu has received research support from Novartis. Dr. Masdeu has received publishing royalties from a publication relating to health care. Dr. Masdeu has received personal compensation in the range of $100,000-$499,999 for serving as a Director, Nantz Nal Alzheimer Center with HOUSTON METHODIST NEUROLOGICAL INSTITUTE.