The coarse‐grained plaque is an Aβ plaque‐type in APOE Ɛ4+ Alzheimer’s disease that is associated with astrogliosis and p‐tau burden

Background The coarse‐grained plaque (CGP) is a divergent plaque‐type recently described in Alzheimer’s disease (AD) 1 . In the current study, we studied the CGPs distribution over the brain, and its association with APOE , p‐tau, and neuroinflammation. Method The cohort (N = 60) was selected from the Mayo Clinic brain bank in Jacksonville, USA. Brain tissue from the frontal ‐, parietal ‐, temporal cortex, and the hippocampus was immunohistochemically stained for Aβ (6F/3D), p‐tau (AT8), CD68, and GFAP. The CGP and classic cored plaque (CCP) were scored as previously described 1 . Total plaque burden was expressed as the sum of all cortical regions. Result The CGP was predominantly located in the neocortex and present in ∼60% of AD cases, who were younger at onset (p<0.05) and had a lower brain weight (p<0.05) than CGP negative cases. When stratified for APOE Ɛ4+ and Ɛ4‐, CGP burden was only in Ɛ4+ positively correlated with p‐tau, Aβ, and GFAP burden in the frontal and parietal cortex (Table 1). CGP burden was not correlated with CD68. The CCP was negatively correlated with p‐tau, and not with GFAP, Aβ or CD68 (Table 1). In APOE Ɛ4+ cases, the burden of CGPs was negatively correlated with the burden of CCPs (Fig.1). Conclusion The neocortical CGP is correlated with increased p‐tau burden and astrogliosis in APOE Ɛ4 + . The CGP is inversely correlated with the common CCP, suggesting an opposite effect of Aβ‐induced tau‐toxicity for the CGP versus the CCP. 1 Boon et al., Acta Neuropathologica, 2020