Neuroinflammation Co-localizes Highly with Tau in Mild Cognitive Impairment from Early Onset Alzheimer's Disease (N4.002).

Objective: To study neuroinflammation in early-onset Alzheimer's disease (AD) and its brain topography, compared with that of tau and amyloid.

Background: Neuroinflammation is a potential therapeutic target in AD. Translocator protein (TSPO) positron emission tomography (PET) is useful to image neuroinflammation, but most "second generation" inflammation tracers cannot image subjects with a low-binder rs6971 genotype. However, participants with any genotype can be imaged with a novel tracer, [11C]ER176, with a high binding potential and more favorable metabolite profile than other TSPO tracers. We postulated that using [11C]ER176 we would be able to detect brain inflammation in mild cognitive impairment (MCI) caused by early-onset AD.

Design/methods: We studied 25 patients with early-onset amnestic MCI and 23 healthy controls, both groups with a similar proportion of all three TSPO-binding affinities. [11C]ER176 total distribution volume (T), obtained with an arterial input function, was determined using voxel-wise and region-wise analyses. Most MCI patients had amyloid (n=23), and tau (n=21) PETs, for which standard uptake value ratios (SUVRs) were calculated using cerebellar grey matter as reference region. Regional correlations among the three tracers were determined for each patient and an average was calculated. All data were corrected for partial volume effect.

Results: In MCI caused by early-onset AD, there was bilateral neuroinflammation in precuneus and lateral temporal and parietal association cortex, and in the right amygdala. The localization of amyloid and tau in the brain were correlated (r= 0.55±0.25), as well as the topography of neuroinflammation and amyloid (0.43±0.22). However, neuroinflammation and tau were even more strongly spatially correlated (r= 0.63 ± 0.24).

Conclusions: Our data highlight the importance of neuroinflammation, a potential therapeutic target, in the AD process. Furthermore, they support the notion that, as shown in experimental tissue and animal models, the propagation of tau in humans is associated with neuroinflammation. Ms. Appleton has nothing to disclose. Quentin Funk has nothing to disclose. Paolo Zanotti Fregonara has nothing to disclose. Meixiang Yu has nothing to disclose. Dr. Faridar has nothing to disclose. Dr. Nakawah has nothing to disclose. Ms. Carrillo has nothing to disclose. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axovant. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Wave LifeSciences. Dr. Dickerson has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Arkuda. Dr. Dickerson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Dr. Dickerson 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 Elsevier. Dr. Dickerson has received publishing royalties from a publication relating to health care. Dr. Dickerson has received publishing royalties from a publication relating to health care. Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Eli Lilly. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alector. Dr. Rabinovici has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Johnson & Joihnson. Dr. Rabinovici has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for JAMA Neurology. The institution of Dr. Rabinovici has received research support from NIH. The institution of Dr. Rabinovici has received research support from American College of Radiology. The institution of Dr. Rabinovici has received research support from Alzheimer's Association. The institution of Dr. Rabinovici has received research support from Rainwater Charitable Foundation. The institution of Dr. Rabinovici has received research support from Genentech. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Topic Chair, Course Director and teacher with AAN. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Grant reviewer with NIH. Dr. Rabinovici has received personal compensation in the range of $500-$4,999 for serving as a Invited speaker with ANA. Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NIH. Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Apostolova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Apostolova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Apostolova has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Apostolova has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Apostolova has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Alzheimer Association. An immediate family member of Dr. Apostolova has stock in Cassava Neurosciences. The institution of Dr. Apostolova has received research support from Roche Diagnostics. The institution of Dr. Apostolova has received research support from NIA. The institution of Dr. Apostolova has received research support from Alzheimer Association. The institution of Dr. Apostolova has received research support from AVID radiopharmaceuticals. The institution of Dr. Apostolova has received research support from Life Molecular Imaging. 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. The institution of Prof. Pascual has received research support from NIH. The institution of Prof. Pascual has received research support from NIH.