title: Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany.
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Varvel
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany.
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Grathwohl
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany.
authors.forename: Karoline
authors.initials: K
authors.lastname: Degenhardt
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Resch
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bosch
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
authors.affiliation: Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, 72076 Tübingen, Germany German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany jonas.neher@uni-tuebingen.de.
authors.forename: Jonas J
authors.initials: JJ
authors.lastname: Neher
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology; D022423:Myeloid Cells / Q000502:physiology*; D011971:Receptors, Immunologic / Q000032:analysis
chemical_list: D016229:Amyloid beta-Peptides; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C498716:Trem2 protein, mouse