| Â | FTLD-Tau | CBD | MAPT | PiD | PSP | FTLD-TDP | Type A | Type B | Type C | Type E | sig. groupa | sig. subtypeb |
|---|
N | 37 | 11 | 5 | 12 | 9 | 55 | 20 | 17 | 13 | 5 | Â | Â |
Female (%) | 16/37 (43.2) | 7/11 (63.6) | 4/5 (80.0) | 4/12 (33.3) | 1/9 (11.1) | 27/55 (49.1) | 11/20 (55.0) | 8/17 (47.1) | 4/13 (30.8) | 4/5 (80.0) | 0.672 | 0.072 |
Phenotype (%) |
 bvFTD | 23/37 (62.2) | 4/11 (36.4) | 5/5 (100) | 10/12 (83.3) | 4/9 (44.4) | 42/55 (76.4) | 14/20 (70.0) | 16/17 (94.1) | 7/13 (53.8) | 5/5 (100.0) | 0.166 | 0.004 |
 PPA | 14/37 (37.8) | 7/11 (63.6) | 0/5 (0) | 2/12 (16.7) | 5/9 (55.6) | 13/55 (23.6) | 6/20 (30.0) | 1/17 (5.9) | 6/13 (46.2) | 0/5 (0) |  |  |
 naPPA | 10/14 (71.4) | 5/7 (71.4) | – | 0/2 (0) | 5/5 (100.0) | 3/13 (23.1) | 2/6 (33.3) | 1/1 (100.0) | 0/6 (0) | – | 0.007 |  < 0.001 |
 svPPA | 1/14 (7.1) | 0/7 (0) | – | 1/2 (50.0) | 0/5 (0) | 8/13 (61.5) | 2/6 (33.3) | 0/1 (0) | 0/6 (0) | – |  |  |
 mPPA | 3/14 (21.4) | 2/7 (28.6) | – | 1/2 (50.0) | 0/5 (0) | 2/13 (15.4) | 2/6 (33.3) | 0/1 (0) | 6/6 (100.0) | – |  |  |
Genetic cases (%) | 5/37 (13.5) | 0/11 (0) | 5/5 (100) | 0/11 (0) | 0/9 (0) | 28/55 (50.9) | 14/20 (70.0)c | 12/17 (70.6) | 2/13 (15.4) | 0/5 (0.0) |  < 0.001 |  |
 MAPT | 5/37 (13.5)d | 0/11 (0) | 5/5 (100) | 0/11 (0) | 0/9 (0) |  |  |  |  |  |  |  |
 C9orf72 |  |  |  |  |  | 15/55 (27.3) | 3/20 (15.0) | 11/17 (64.7) | 1/13 (7.7) | 0/5 (0.0) |  |  < 0.001g |
 GRN |  |  |  |  |  | 11/55 (20.0)e | 10/20 (50.0) | 1/17 (5.9) | 0/13 (0.0) | 0/5 (0.0) |  |  |
 TBK1 |  |  |  |  |  | 2/55 (3.6)f | 1/20 (5.0) | 0/17 (0.0) | 1/13 (7.7) | 0/5 (0.0) |  |  |
Age at onset | 60.0 ± 12.3 | 58.1 ± 9.4# | 47.0 ± 14.9# | 56.8 ± 6.8# | 73.6 ± 7.7 | 59.0 ± 7.7 | 60.4 ± 6.4# | 57.7 ± 8.8# | 59.2 ± 8.5# | 57.6 ± 8.4# | 0.691 |  < 0.001 |
Age at death | 67.6 ± 12.5 | 64.4 ± 10.6# | 53.8 ± 16.0# | 67.3 ± 8.3 | 79.6 ± 7 | 66.0 ± 8.8 | 67.5 ± 7.1# | 63.7 ± 9.2# | 68.9 ± 9.9 | 60.0 ± 9.1# | 0.496 |  < 0.001 |
Disease duration | 7.6 ± 3.7 | 6.3 ± 2.9 | 6.8 ± 2.3 | 10.5 ± 4.2^& | 6.0 ± 2.5 | 6.9 ± 4.3 | 7.1 ± 3.6 | 6.0 ± 4.8 | 9.6 ± 3.7& | 2.4 ± 0.9 | 0.394 |  < 0.001 |
PMI | 12.0 ± 6.4 | 13.9 ± 7.4 | 9.4 ± 3.1 | 12.6 ± 6.4 | 10.6 ± 6.5 | 12.6 ± 6.6 | 10.6 ± 5.9 | 14.4 ± 7.7 | 13.8 ± 6.0 | 11.6 ± 6.8 | 0.689 | 0.550 |
Brain weight | 1091.9 ± 146.7 | 1096.0 ± 140.7 | 1082.0 ± 192.7 | 1021.5 ± 126.5 | 1179.0 ± 123.3 | 1097.7 ± 190.3 | 985.9 ± 165.1& | 1145.0 ± 207.3 | 1126.0 ± 134.1 | 1289.0 ± 119.7 | 0.872 | 0.004 |
- bvFTD = behavioral variant of frontotemporal dementia; CBD = corticobasal degeneration; FTLD-Tau = frontotemporal lobar degeneration with inclusions of the protein tau; FTLD-TDP = frontotemporal lobar degeneration with inclusions of the TDP-43 protein; MAPT = FTLD-tau with MAPT gene mutation; mPPA = mixed variant of primary progressive aphasia; naPPA = nonfluent variant of primary progressive aphasia; PiD = Pick’s disease; PMI = post-mortem interval; PPA = primary progressive aphasia; PSP = progressive supranuclear palsy; svPPA = semantic variant of primary progressive aphasia; Type A/Type B/Type C/Type E = subtypes of FTLD-TDP
- aStatistical significance (p value) when comparing the two main FTLD proteinopathies (i.e. FTLD-Tau and FTLD-TDP)
- bStatistical significance (p value) when comparing all proteinopathy subtypes (i.e. FTLD-Tau: CBD, MAPT, PiD, PSP; FTLD-TDP: type A, type B, type C, type E)
- cOne patient with FTLD-TDP type A had two VUS in the GRN gene (GRN c.956 T > A, p.Ile319Lys; c.1058G > A, p.Ser353Asn), which were not considered to be pathogenic; therefore, this patient was classified as a sporadic case. Another patient with FTLD-TDP type A had a mutation in the GBE gene (GBE1 c.1280delG, p.G427fs*9), whose association with FTLD-TDP is unclear; for this reason, this patient was also classified as a sporadic case
- dMAPT point mutations were: c.1165G > A, p.G389R (n = 1); c.796C > G, p.L266V (n = 1); c.902C > T, p.P301L (n = 1); c.915 + 16C > T, intronic variant (n = 2)
- eGRN point mutations were: c.1009C > T, p.Q337* (n = 1 type A); c.102delC, p.G35Efs*19 (n = 1 type A); c.1179 + 2 T > C, p.? (n = 1 type B); c.1252C > T, p.R418* (n = 1 type A); c.1414-2A > G, p.A472Vfs*10 (n = 1 type A); c.1477C > T, p.R493* (n = 1 type A); c.26C > A, p.A9D (n = 1 type A); c.295_308delTGCCCACGGGGCTT, p.C99Pfs*15 (n = 1 type A); c.348A > C, p.S116 = (n = 1 type A); c.675_676delCA, p.S226Wfs*28 (n = 1 type A); c.911G > A, p.W304* (n = 1 type A)
- fTBK1 point mutations were: c.1387_1388delGA, p.E463Sfs*13 (n = 1 type C); TBK1 c.922C > T, p.R308* (n = 1 type A)
- gThe frequency of FTLD-TDP-related genetic mutations (i.e. C9orf72, GRN, TBK1) was compared between proteinopathy subtypes of FTLD-TDP only (i.e. type A, type B, type C, type E). The frequency of FTLD-Tau-related genetic mutations (i.e. MAPT) could not be statistically tested between subtypes because all cases with mutation were grouped as a separate MAPT proteinopathy subtype
- #< 0.05 compared to PSP (post-hoc comparisons, Bonferroni-corrected); ^< 0.05 compared to TDP type B (post-hoc comparisons, Bonferroni-corrected); &< 0.01 compared to TDP type E (post-hoc comparisons, Bonferroni-corrected)
