Introduction
Materials and methods
Human cases
Male: femalea | Mean age in years (SD)b | Neuro-pathological diagnosis | Number of cases available | Mutations | |||||
---|---|---|---|---|---|---|---|---|---|
Pineal gland | Hypo-thalamusc | SCN-related neurons | SON | PVN | |||||
C9orf72 cases | 6:1 | 56.7 (4.8) | ALS | 4 | 4 | 3 | 3 | 3 | C9orf72 |
FTLD-TDP | 2 | 2 | 2 | 2 | 2 | C9orf72 | |||
ALS-FTLD | 0 | 1 | 1 | 1 | 1 | C9orf72 | |||
Total | 6 | 7 | 6 | 6 | 6 | / | |||
nonC9orf72 cases | 13:8 | 62.1 (11.2) | ALS | 9 | 11 | 2 | 6 | 7 | 10 no mutation, 1 TARDBP |
FTLD-TDP | 7 | 9 | 2 | 6 | 7 | 5 no mutation, 1 TUBA4A, 1 GRN, 1 VCP, 1 TBK1 | |||
ALS-FTLD | 1 | 1 | 1 | 1 | 1 | No mutation | |||
Total | 17 | 21 | 5 | 13 | 15 | / | |||
Healthy control cases | 2:1 | 63.0 (2.7) | Healthy control | 3 | 3 | 0 | 0 | 0 | No mutation |
Total | 3 | 3 | 0 | 0 | 0 | / |
Immunohistochemistry
Microscopic assessment
Statistical analysis
Results
Abundant DPR pathology in the pineal gland of C9orf72 cases
C9orf72 ALS and/or FTLD-TDP cases | nonC9orf72 ALS and/or FTLD-TDP cases | Healthy control cases | ||||
---|---|---|---|---|---|---|
Pineal gland | Number of positive cases | Median score (IQR, range) | Number of positive cases | Median score (IQR, range) | Number of positive cases | Median score (IQR, range) |
Poly(GA) | 6/6 (100%) (p < 0.0001)a | 4 (1; 2–4) | 0/17 (0%) | 0 (0; 0–0) | 0/3 (0%) | 0 (0; 0–0) |
Poly(GP) | 3/3 (100%) 3 n.a.c | 4 (3; 1–4) | n.a.d | n.a.d | n.a.d | n.a.d |
Poly(GR) | 3/3 (100%) 3 n.a.c | 1 (1; 1–2) | n.a.d | n.a.d | n.a.d | n.a.d |
Poly(PR) | 2/3 (67%) 3 n.a.c | 1 (1; 0–1) | n.a.d | n.a.d | n.a.d | n.a.d |
pTDP-43 | 0/6 (100%) b | 0 (0; 0–0) | 0/17 (0%) | 0 (0; 0–0) | 0/3 (0%) | 0 (0; 0–0) |
Hypothalamus | Number of positive cases | Median score (IQR, range) | Number of positive cases | Median score (IQR, range) | Number of positive cases | Median score (IQR, range) |
Poly(GA) | 7/7 (100%) | n.a.e | 0/21 (0%) | n.a.e | 0/3 (0%) | n.a.e |
pTDP-43 | 4/7 (57%) | n.a.e | 15/21 (71%) | n.a.e | 0/3 (0%) | n.a.e |
SCN-related neurons | Number of positive cases | Mean % (SD) VIP-ir neurons affected | Number of positive cases | Mean % (SD) VIP-ir neurons affected | Number of positive cases | Mean % (SD) VIP-ir neurons affected |
Poly(GA) | 3/6 (50%) (p = 0.1818) a | 8.5 (10.6) | 0/5 (0%) | 0.0 (0.0) | n.a. | n.a. |
pTDP-43 | 0/6 (0%) b | 0.0 (0.0) | 0/5 (0%) | 0.0 (0.0) | n.a. | n.a. |
SON magno-cellular cells | Number of positive cases | Median score (IQR, range) | Number of positive cases | Median score (IQR, range) | Number of positive cases | Median score (IQR, range) |
Poly(GA) | 0/6 (0%) b | 0 (0; 0–0) | 0/13 (0%) | 0 (0; 0–0) | n.a. | n.a. |
pTDP-43 | 0/6 (0%) b | 0 (0; 0–0) | 0/13 (0%) | 0 (0; 0–0) | n.a. | n.a. |
PVN magnocellular cells | Number of positive cases | Median score (IQR, range) | Number of positive cases | Median score (IQR, range) | Number of positive cases | Median score (IQR, range) |
Poly(GA) | 0/6 (0%) b | 0 (0; 0–0) | 0/15 (0%) | 0 (0; 0–0) | n.a. | n.a. |
pTDP-43 | 0/6 (0%) b | 0 (0; 0–0) | 0/15 (0%) | 0 (0; 0–0) | n.a. | n.a. |