title: Proliferation in the Alzheimer hippocampus is due to microglia, not astroglia, and occurs at sites of amyloid deposition.
abstract: Microglia and astrocytes contribute to Alzheimer's disease (AD) etiology and may mediate early neuroinflammatory responses. Despite their possible role in disease progression and despite the fact that they can respond to amyloid deposition in model systems, little is known about whether astro- or microglia can undergo proliferation in AD and whether this is related to the clinical symptoms or to local neuropathological changes. Previously, proliferation was found to be increased in glia-rich regions of the presenile hippocampus. Since their phenotype was unknown, we here used two novel triple-immunohistochemical protocols to study proliferation in astro- or microglia in relation to amyloid pathology. We selected different age-matched cohorts to study whether proliferative changes relate to clinical severity or to neuropathological changes. Proliferating cells were found across the hippocampus but never in mature neurons or astrocytes. Almost all proliferating cells were co-labeled with Iba1+, indicating that particularly microglia contribute to proliferation in AD. Proliferating Iba1+ cells was specifically seen within the borders of amyloid plaques, indicative of an active involvement in, or response to, plaque accumulation. Thus, consistent with animal studies, proliferation in the AD hippocampus is due to microglia, occurs in close proximity of plaque pathology, and may contribute to the neuroinflammation common in AD.
authors.affiliation: Swammerdam Institute for Life Sciences-Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Marlatt
authors.affiliation: Department of Neuroimmunology, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090 Vienna, Austria.
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Department of Neuropathology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.affiliation: Department of Pathology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Elise S
authors.initials: ES
authors.lastname: van Haastert
authors.affiliation: Department of Pathology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Jeroen J M
authors.initials: JJ
authors.lastname: Hoozemans
authors.affiliation: Swammerdam Institute for Life Sciences-Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands ; Department of Neuroscience and Pharmacology, University Medical Center Utrecht, P.O. Box 85060, 3508 AB Utrecht, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Joels
authors.affiliation: Swammerdam Institute for Life Sciences-Center for Neuroscience, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Lucassen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D001253:Astrocytes / Q000502:physiology*; D049109:Cell Proliferation; D005260:Female; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D017628:Microglia / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D058225:Plaque, Amyloid / Q000473:pathology