TY  - JOUR
AU  - Varvel, Nicholas H
AU  - Grathwohl, Stefan A
AU  - Degenhardt, Karoline
AU  - Resch, Claudia
AU  - Bosch, Andrea
AU  - Jucker, Mathias
AU  - Neher, Jonas J
TI  - Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer's disease.
JO  - Journal of experimental medicine
VL  - 212
IS  - 11
SN  - 1540-9538
CY  - New York, NY
PB  - Rockefeller Univ. Press
M1  - DZNE-2020-04608
SP  - 1803-1809
PY  - 2015
AB  - Immune cells of myeloid lineage are encountered in the Alzheimer's disease (AD) brain, where they cluster around amyloid-β plaques. However, assigning functional roles to myeloid cell subtypes has been problematic, and the potential for peripheral myeloid cells to alleviate AD pathology remains unclear. Therefore, we asked whether replacement of brain-resident myeloid cells with peripheral monocytes alters amyloid deposition in two mouse models of cerebral β-amyloidosis (APP23 and APPPS1). Interestingly, early after repopulation, infiltrating monocytes neither clustered around plaques nor showed Trem2 expression. However, with increasing time in the brain, infiltrating monocytes became plaque associated and also Trem2 positive. Strikingly, however, monocyte repopulation for up to 6 mo did not modify amyloid load in either model, independent of the stage of pathology at the time of repopulation. Our results argue against a long-term role of peripheral monocytes that is sufficiently distinct from microglial function to modify cerebral β-amyloidosis. Therefore, myeloid replacement by itself is not likely to be effective as a therapeutic approach for AD.
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: pathology
KW  - Alzheimer Disease: therapy
KW  - Amyloid beta-Peptides: metabolism
KW  - Animals
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - Disease Models, Animal
KW  - Female
KW  - Male
KW  - Membrane Glycoproteins: analysis
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Monocytes: physiology
KW  - Myeloid Cells: physiology
KW  - Receptors, Immunologic: analysis
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Membrane Glycoproteins (NLM Chemicals)
KW  - Receptors, Immunologic (NLM Chemicals)
KW  - Trem2 protein, mouse (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26458770
C2  - pmc:PMC4612086
DO  - DOI:10.1084/jem.20150478
UR  - https://pub.dzne.de/record/138286
ER  -