1H‐MRS signature in Alzheimer disease in Down syndrome

Abstract

AbstractBackgroundDown syndrome(DS) is a genetically determined form of Alzheimer's Disease(AD). Proton magnetic resonance spectroscopy(1H‐MRS) allows in vivo assessment of brain biochemistry. Few studies have assessed 1H‐MRS metabolites for tracking AD in DS. Our objective was to assess the changes in the myo‐inositol(mI)–a glial marker‐ and N‐acetyl‐aspartate(NAA)‐ a neuronal marker‐ in 1H‐MRS and its correlation with cortical thickness and AD biochemical biomarkers in the AD continuum in DS.MethodCross‐sectional study. DS subjects were classified into asymptomatic (aDS) and symptomatic: prodromal AD(pDS) and AD dementia(dDS).Participants underwent a single‐voxel 3TMRS in the posterior cingulate/precuneus and a 3Tstructural MRI. mI, NAA and total creatine (TCr) metabolites levels were quantified using Tarquin. Cortical thickness (CTh) values were computed using Freesurfer. Aβ1‐42, total tau, phosphotau, and NFL levels were determined in plasma using a SIMOA platform and in CSF using Lumipulse. For a subset of subjects, amyloid plaques were spatially mapped using Florbetapir‐PET (PET‐FBP). We performed ANCOVA analyses with Tukey posthoc corrections to assess the mI/TCr and the NAA/TCr between‐groups differences. We computed the vertex‐wise correlation between mI/TCr, NAA/TCr and CTh. We used linear regression to assess relationship between MRS metabolites and PET‐FBT and AD biochemical biomarkers.ResultWe included 83 adults with DS(61aDS, 15pDS and 7dDS) and 25 euploid healthy controls (HC). The three DS subgroups showed significant (p<0.05) increases in mI/TCr when compared to HC. Moreover, we found a gradient of increases of mI/TCr in the DS subgroups (aDS>pDS=dDS). The dDS subgroup showed significant (p<0.05) decrease in NAA/Cr compared to HC and aDS. mI/TCr levels were negatively correlated with CTh in the medial and lateral temporal regions, bilaterally. NAA/TCr levels revealed a similar pattern of positive correlations with Cth but more widespread. mI/TCr levels were positively correlated with PET‐FBP and plasmatic NfL in the DS symptomatic group. NAA/TCr level were negatively correlated with CSF tTau and plasmatic NfL in the DS symptomatic group.ConclusionThere is a gradient of increases of myo‐inositol in the AD continuum in DS which correlate with atrophy in temporal regions, increased PET‐FBP, and plasma NfL. Our data reveals a 1H‐MRS signature in AD in DS and supports myo‐inositol as a potential glial marker.