Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer's disease
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Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer's disease. / Varvel, Nicholas H; Grathwohl, Stefan A; Degenhardt, Karoline; Resch, Claudia; Bosch, Andrea; Jucker, Mathias; Neher, Jonas J.
In: J EXP MED, Vol. 212, No. 11, 19.10.2015, p. 1803-9.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer's disease
AU - Varvel, Nicholas H
AU - Grathwohl, Stefan A
AU - Degenhardt, Karoline
AU - Resch, Claudia
AU - Bosch, Andrea
AU - Jucker, Mathias
AU - Neher, Jonas J
N1 - © 2015 Varvel et al.
PY - 2015/10/19
Y1 - 2015/10/19
N2 - 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.
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 - Amyloid beta-Peptides/metabolism
KW - Animals
KW - Brain/metabolism
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
U2 - 10.1084/jem.20150478
DO - 10.1084/jem.20150478
M3 - SCORING: Journal article
C2 - 26458770
VL - 212
SP - 1803
EP - 1809
JO - J EXP MED
JF - J EXP MED
SN - 0022-1007
IS - 11
ER -
