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Brain iron accumulation has been found to accelerate disease progression in amyloid-β(Aβ) positive Alzheimer patients, though the mechanism is still unknown. Microglia have been identified as key players in the disease pathogenesis, and are highly reactive cells responding to aberrations such as increased iron levels. Therefore, using histological methods, multispectral immunofluorescence and an automated in-house developed microglia segmentation and analysis pipeline, we studied the occurrence of iron-accumulating microglia and the effect on its activation state in human Alzheimer brains. We identified a subset of microglia with increased expression of the iron storage protein ferritin light chain (FTL), together with increased Iba1 expression, decreased TMEM119 and P2RY12 expression. This activated microglia subset represented iron-accumulating microglia and appeared morphologically dystrophic. Multispectral immunofluorescence allowed for spatial analysis of FTL + Iba1 + -microglia, which were found to be the predominant Aβ-plaque infiltrating microglia. Finally, an increase of FTL + Iba1 + -microglia was seen in patients with high Aβ load and Tau load. These findings suggest iron to be taken up by microglia and to influence the functional phenotype of these cells, especially in conjunction with Aβ.

Background: Evaluating inflammatory changes over time on MR images of the spine in patients with suspected axial Spondyloarthritis (axSpA) can be a labor-intensive task, requiring readers to manually search for and perceptually align a set of vertebrae between two scans. The purpose of this study was to assess the feasibility of computer-aided (CA) evaluation of such inflammatory changes in a framework where scans from two time points are fused into a single color-encoded image integrated into an interactive scoring tool., Methods: For 30 patients from the SPondyloArthritis Caught Early (SPACE) cohort (back pain ≥ 3 months, ≤ 2 years, onset < 45 years), baseline and follow-up MR scans acquired 9-12 months apart were fused into a single color-encoded image through locally-rigid image registration to evaluate inflammatory changes in 23 vertebral units (VUs). Scoring was performed by two expert readers on a (-2, 2) scale using an interactive scoring tool. For comparison of direction of change (increase/decrease) indicated by an existing reference, Berlin method scores ((-3, 3) scale) of the same MR scans from a different ongoing study were used. The distributions of VU-level differences between CA readers and between the CA and Berlin methods (sign of change scores) across patients were analyzed descriptively. Patient-level agreement between CA readers was assessed by intraclass correlation coefficient (ICC)., Results: Five patients were excluded from evaluation due to failed vertebrae segmentation. Patient-level inter-reader agreement ICC was 0.56 (95% CI: 0.22 to 0.78). Mean VU-level inter-reader differences across 25 patients ranged (-0.04, 0.12) with SD range (0, 0.45). Across all VUs, inter-reader differences ranged (-1, 1) in 573/575 VUs (99.7%). Mean VU-level inter-method differences across patients ranged (-0.04, 0.08) with SD range (0, 0.61). Across all VUs, inter-method differences ranged (-1, 1) in 572/575 VUs (99.5%)., Conclusions: Fusion of MR scans of the spine from two time points into a single color-encoded image allows for direct visualization and measurement of inflammatory changes over time in patients with suspected axSpA.