Fig. 10. TMEM106B risk allele is associated with increased myelin loss and reduced microglial numbers in humans.

(A to C) Corpus callosum sections of postmortem human brain tissues (table S1) were stained with MBP and IBA1 antibodies. Scale bar, 100 μm. Five to ten 20× images were taken from each section. IBA1-positive microglia number per image and MBP levels were quantified in (B) and (C), respectively. MBP intensity was normalized to the average of AA samples. Data represent the means ± SEM. Statistical significance was analyzed by unpaired two-tailed Student’s t test (n = 6 to 7 for each genotype). *P < 0.05. (D) A model to illustrate the function of TMEM106B in microglia and myelination: Dysfunction of TMEM106B in microglia leads to decreased levels of TREM2, lysosomal abnormalities, and other defects; these alterations result in reduced microglia survival and proliferation in response to myelin debris, contributing to myelination deficits.