In contrast, the analysis of the Knight-ADRC brains showed that the neuronal relative proportion decrease is less pronounced in TREM2 carriers than in other LOAD cases. We replicated this finding in a multi-area analysis from the MSBB dataset. These results may implicate that TREM2 risk variants lead to a cascade of pathological events that differ from those occurring in sporadic AD cases, which is also consistent with the known biology of TREM2. Further longitudinal neuroimaging analysis is required to validate our findings. TREM2 is involved in AD pathology through microglia mediated pathways, implicated on altered immune response and inflammation [71]. Recent studies in TREM2 knock-out animals showed that fewer microglia cells were found surrounding Aβ plaques with impaired microgliosis [72]. Furthermore, TREM2 deficiency was reported to attenuate tauopathy against brain atrophy [73]. We found no significant difference in the proportion of microglia between AD cases and controls. However, we found significantly decreased microglia in brains exhibiting PA (Additional file 1: Table S7; Additional file 1: Figure S6), proving that these studies are sufficiently powered to identify significant differences. In any
