Differential associations between AV-45 brain amyloid and blood biomarkers by consensus diagnosis among adults with Down Syndrome
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Authors: Leah Goehring, Melissa Petersen, Michael Phelan, Lisa Taylor, Anne Fagan, Rachel Henson, Beau Ances, Nicole Schupf, Michael Yassa, Sharon Krinsky-McHale, Mark Mapstone, Florence Lai, H. Diana Rosas, Margaret Pulsifer, Christie Hom, Wayne Silverman, Ira Lott & David Keator Introduction: Individuals with Down Syndrome (DS) are at an increased risk for developing dementia, specifically Alzheimer's Disease (AD) due to triplication of Chromosome 21 leading to the overproduction of the beta amyloid. Few studies to date have examined the link between plasma biomarkers of AD pathology and brain amyloid in adults with DS who also have dementia. The aim of this study is to examine the relationship between specific plasma biomarkers (neurofilament light chain [NfL], total tau) and amyloid deposition in the brain among adults with DS. Methods: Data were analyzed on n=66 adults with DS (n=41 cognitively stable [CS]; n=16 mild cognitive impairment [MCI-DS]; n=9 dementia [DEM]) enrolled in the Alzheimer's Disease in Down Syndrome (ADDS) Study. Plasma concentrations of NfL and total tau were analyzed using Single Molecule Array (Simoa) technology.18F-AV-45 PET and T1-weighted MRI scans were collected to examine amyloid deposition in the brain. MRI-derived voxel-weighted SUVR averages were derived for each region of interest (ROI). A priori selected brain regions included the anterior/posterior cingulate, superior/inferior/middle temporal, superior frontal, inferior parietal, lateral occipital, orbitofrontal, lateral/medial orbitofrontal, and rostral middle frontal lobes. Fixed effect linear models were conducted with each diagnostic group to examine the association between the predictor variables (plasma biomarkers) with each of the a prior-identified ROIs, adjusting for linear effects of the covariates (age, ApoEe4, site, sex and brain volume). Results: Among those with DS who were determined to be CS, elevations in NfL were significantly associated with increased amyloid uptake in the superior temporal lobe, anterior cingulate, superior frontal lobe, inferior parietal lobe, inferior temporal lobe, orbitofrontal lobe, middle temporal lobe, lateral orbitofrontal lobe, medial orbitofrontal lobe and rostral middle frontal lobe. The latter ROI was also found to be significantly related to increased NfL levels among those with MCI-DS. No significant associations were found between NfL and amyloid deposition among any of the ROI examined for those with DEM. When examining the link between total tau and amyloid, the only finding was for those with a diagnosis of DEM, with a decrease in total tau found to be significantly associated with increased amyloid in the superior temporal lobe. Total tau was otherwise not found to be significantly related to amyloid deposition in any of the ROI for those with a diagnosis of CS or MCI. Discussion: Plasma biomarkers remain an appealing tool as they are less expensive and invasive as compared to other neuro-diagnostic modalities. Our study suggests that plasma biomarkers may be useful in tracking amyloid deposition in specific regions of the brain for adults with DS and highlight the potential utility for their application.