Iron loading is a prominent feature of activated microglia in Alzheimer’s disease patients

Acta Neuropathologica Communications

Willeke M. C. van Roon-Mom¹  Boyd Kenkhuis²  Louise van der Weerd²  Marieke E. IJsselsteijn³  Lorraine de Haan³  Noel F. C. C. de Miranda³  Boudewijn P. F. Lelieveldt⁴  Antonios Somarakis⁴  Jouke Dijkstra⁴  Oleh Dzyubachyk⁵  Thomas Höllt⁶ 

[1] Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands;Department of Human Genetics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands;Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands;Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands;Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands;Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands;Department of Cell and Chemical Biology, Leiden University Medical Center, Leiden, The Netherlands;Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands;Department of Intelligent Systems, Delft University of Technology, Delft, The Netherlands;

关键词: Alzheimer;    Microglia;    Iron;    Ferritin;    Human;   

DOI  :  10.1186/s40478-021-01126-5

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY