Emerging evidence suggests a link between neuroinflammation and beta-amyloid (A β) deposition in Alzheimer's disease (AD). Our recent in vivo microPET study showed higher 11 C-AZD2184 binding in 18-24 months APPswe mice, while elevated 11 C-deuterium-L-deprenyl binding in 6 months APPswe mice, suggesting different time courses of pathological events (Rodriguez-Vieitez, AAIC 2013). Here we investigate further the temporal and regionalrelation of astrocytosis, microgliosis and A β deposition in APPswe mice in vitro by autoradiography alsong with immunostaining. Binding characteristics of 3 H-AZD2184, 3 H-PIB, 3 H-L-deprenyl and 3 H-PK11195 were evaluated in APPswe mice brain. Distribution of Aβ, astrocytosis and microgliosis in APPswe mice (6, 8-15, 18-24 months, n=3-6/group) and wild-type mice (8-12, 18-24 months, n=3-6/group) were analyzed by in vitro autoradiography using the aforementioned ligands and immunostaining performed with antibodies for Aβ 42, GFAP, Iba-1 in sagittal brain slides. 3 H-AZD2184, 3 H-PIB, 3 H-L-deprenyl and 3 H-PK11195 autoradiography revealed presence of high affinity binding sites (nM range) in APPswe mice cortex. Both the 3 H-AZD2184 and 3 H-PIB binding wereelevated in the cortex and hippocampus of 18-24 months APPswe mice compared to wild-type mice, corroborated with increased A β 42 plaque deposition observed in aged APPswe mice. The 3 H-L-deprenyl binding was high already in youngAPPswemice and demonstrated no changes with age, while the 3 H-PK11195 binding was increased in the hippocampus of aged APPswe mice. A greater number of hypertrophic GFAP+ astrocytes were surrounding and distant to A β plaques, whereas Iba1+ activated microglia were in close proximity to A β plaques in aged APPswe mice. Our findings demonstrate that astrocytosis precedes amyloid deposition, and that microgliosis is more closely associated with A β plaque deposition in APPswe mice brain, supporting our in vivo microPET finding of early astrocytosis in APPswe mice.
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Ni et al. (2014) studied this question.