Disrupted structural connectivity in ArcAβ mouse model of Aβ amyloidosis

摘要: Although amyloid beta (Aβ) deposition is one of the major causes white matter (WM) alterations in Alzheimer9s disease (AD), little known about underlying basis WM damage and its association with global structural connectivity network topology. We aimed to dissect contributions microstructure properties ArcAβ mice model Aβ amyloidosis. acquired diffusion-weighted images (DWI) wild type (WT) transgenic (TG) using a 9.4 T MRI scanner. Fixel-based analysis (FBA) was performed measure fiber tract-specific properties. also three complementary experiments; identify differences connectivity, compute cellular alterations. Transgenic displayed disrupted centered entorhinal cortex (EC) lower density bundle cross-section. In addition, there reduced efficiency degree centrality weighted mice. To further examine neuronal deficits, we histology experiments. found no alteration myelination an increased level neurofilament light (NFL) brain regions TG Furthermore, had number perineuronal nets (PNN) EC. The observed FDC reductions may indicate decrease axonal diameter or axon count which would explain deficits increase NFL suggests breakdown integrity, reduce health. Considering pivotal role EC AD, primarily release, damaging PNN pathway, resulting connectivity.