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Fig. 7 | Acta Neuropathologica Communications

Fig. 7

From: TREM2 modulates differential deposition of modified and non-modified Aβ species in extracellular plaques and intraneuronal deposits

Fig. 7

Differential deposition of phosphorylated Aβ species in human brains with the common and rare variants of TREM2. a Temporal neocortex of human AD patients with the indicated TREM2 variants (see Table 2) stained to detect total Aβ (with 4G8), nmAβ, and pSer8-Aβ on consecutive sections. Immunostaining clearly indicated decreased deposition of N-terminally non-modified Aβ species in the TREM2 variants. pSer8-Aβ stained the plaques along with vascular as well as intracellular deposits. (Scale bar = 200 μm, 20×, the magnified dotted 4 red boxes within ROI and the small square boxes of 120 × 120 µm on the right-side (for plaques and vessels) represents deposition characteristics on consecutive sections except the square box of 45 × 45 µm for the neuronal deposits). b–c Quantification of the number of plaques (t(6.997) = 2.378, *p = 0.0490) and percent plaque load (t(7.786) = 2.412, *p = 0.0432) stained with 4G8 antibody in the analyzed ROIs of TREM2 risk allele carriers (Plaque area cutoff = 10 µm2, n = 6 cases each for TREM2 variants and CV, unpaired t-test with Welch's correction). d Box and whiskers plot showing a significant increase in the plaque size of TREM2 variants compared to CV cases (n = 68,631 (CV) and n = 88,835 (TREM2 variants), ****p < 0.0001, Mann–Whitney test. Additional data are provided in Additional file 1: Figure S8b-c. e, f Quantification of the numbers of plaques (t(6.96) = 0.3754, nsp = 0.7185) and the percent plaque load (t(4.366) = 0.5145, nsp = 0.6319) stained with pSer8-Aβ antibody in the analyzed ROIs of TREM2 risk allele carriers (Plaque area cutoff = 30 µm2, n = 5 cases for TREM2 variants and n = 6 cases for CV, unpaired t-test with Welch's correction). Case#3, with highest fixation time, was omitted for the plaque count and size quantification as it was difficult to identify extracellular plaques stained with 1E4E11 (pSer8-Aβ) antibody. g Box and whiskers plot showing a significant decrease in the plaque size of TREM2 variants compared to CV cases (n = 17,456 (CV) and 13,291 (TREM2 variants), ****p < 0.0001, Mann–Whitney test. Additional data are provided in Additional file 1: Figure S8d-e. There was a significant increase of intracellular deposits of h nmAβ (t(9.138) = 2.429, *p = 0.0377) and i pSer8-Aβ (t(9.389) = 2.251, *p = 0.0497) in the analyzed cortical ROIs of TREM2 variant as compared to CV cases (n = 6 cases each for TREM2 variants and CV, unpaired t-test with Welch's correction). No data or numerical value was excluded unless otherwise stated. Each colored dot with respective gender symbol represents single case. Except for bot and whiskers plot, all data represent mean ± SEM

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