Fig. 4: Amyloid-β neuritic plaque density correlates with increased MF-ADNC tau seeding activity and PTMs. | Nature Communications

Fig. 4: Amyloid-β neuritic plaque density correlates with increased MF-ADNC tau seeding activity and PTMs.

From: Early Alzheimer’s Disease with frequent neuritic plaques harbors neocortical tau seeds distinct from primary age-related tauopathy

Fig. 4: Amyloid-β neuritic plaque density correlates with increased MF-ADNC tau seeding activity and PTMs.

a Tau brain homogenate (BH) log10SD50s (average across 1-3 replicate endpoint dilution analyses) from all cases organized by neuropathological staging of tau (Braak stages, II: n = 16, III: n = 10, IV: n = 12) and Aβ (CERAD scores 0: n = 12, 1: n = 6, 2: n = 14, 3: n = 6 and Thal phases 0: n = 9, 1-2: n = 8, 3: n = 2, 4-5: n = 19). Center line represents mean, while error bars correspond to standard deviation. Statistical significance depicted corresponds to Tukey’s Honest Significant Difference (HSD) test, employed as a post-hoc test when an overall ANOVA demonstrated significance differences for MF seeding by Thal phase (F = 4.1, p = 0.01) and CERAD score (F = 14.6, p = 2.8 × 10-6), as well as HP seeding by Braak stage (F = 5.4, p = 0.009). b Representative BH (5% w/v) and SI extract (0.1 mg/mL) tau PTM Western blots of Braak IV cases across CERAD scores 1-3. A high ADNC (Thal 5, Braak VI, CERAD 3) sample is included as a positive control. Similar results have been obtained across 3+ technical replicates. c Representative pS202/pT205 tau and Aβ immunohistochemistry (IHC) staining (brown) of Braak IV cases across CERAD scores 1-3. (Scale bar = 100 μM). d–f Tau PTM immunoreactivities of MF BH normalized to total protein staining of individual cases (averages across 3 replicates) grouped by CERAD scores (0: n = 12, 1: n = 6, 2: n = 14, 3: n = 6). Bars represent group means and error bars are standard deviations across the averaged replicate values. A high ADNC group (n = 3) is included for comparison but was not included in statistical analyses (demographics detailed in Supplementary Table 1). Statistical significance depicted corresponds to Tukey’s HSD test, employed as a post-hoc test when an overall ANOVA demonstrated significance differences for MF pS202/T205 (F = 9.2, p = 1.3 × 10-4), pT217 (F = 7.4, p = 6.0 × 10−4), and C-term (F = 4.3, p = 0.01). Possible (pos., n = 8) and definite (def., n = 9) PART subgroups are as indicated. All statistical tests in this figure are two-sided, when applicable to the test type.

Back to article page