Multimodal imaging of microstructural cerebral changes and loss of synaptic density in Alzheimer’s disease

Background:
Multiple neuropathological changes are involved in Alzheimer’s disease (AD) progression. The hallmark biomarkers are amyloid-beta, tau pathology, neuronal and synaptic loss. Other potential biomarkers, such as the level of iron and myelin content in the brain, have not been thoroughly studied. Nevertheless, these can be estimated in vivo thanks to tissue magnetic resonance (MR) properties measured through quantitative MR imaging (qMRI) techniques.
Aim:
We aimed to assess the co-occurrence of neurodegeneration (as measured with synaptic density), increased iron content and decreased myelin content in Alzheimer’s disease.
Method:
Data include 24 amyloid-positive Alzheimers patients (AD-11/13 males/females) and 19 healthy controls (HC-9/11 males/females). They underwent a multiparameter qMRI protocol used to generate quantitative maps sensitive to microstructural changes in myelin, iron deposits, and water content in grey matter (GM). Synaptic density was indexed by [18F]UCB-H-PET imaging using the distribution volume density (VT) maps. First, we applied univariate statistical analyses to investigate variation between AD and HC groups for each modality individually. Then, a multivariate GLM approach was used to compare the two groups pooling all modalities.
Results/Conclusions:
In GM univariate analyses, there was no significant difference between the AD and HC groups in any map at corrected statistical threshold. Conversely, the multivariate analysis on GM, combining MT, R2s, and synaptic density, provided significant group differences (FWEcorr P-value < 0.05) see figure 1. These variations are observed in the right amygdala (at voxel level) and in 5 distinct clusters covering the bilateral anterior hippocampal structures. These show that patients with AD present convergence of neuropathological changes in the hippocampal area, suggesting that different pathological mechanisms co-exist in areas known to harbor early-stage neuronal death.