Circadian sleep/wake-associated cells show dipeptide repeat protein aggregates in C9orf72-related ALS and FTLD cases

Dedeene, Lieselot; Van Schoor, Evelien; Vandenberghe, Rik; Van Damme, Philip; Poesen, Koen; Thal, Dietmar Rudolf

doi:10.1186/s40478-019-0845-9

Table 2 Neuropathological analysis of the investigated brain regions

From: Circadian sleep/wake-associated cells show dipeptide repeat protein aggregates in C9orf72-related ALS and FTLD 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.

^a p-values of Mann-Whitney test are shown for comparison of poly(GA) pathology between the C9orf72 and the nonC9orf72 ALS and/or FTLD-TDP cases as a reference
^b No statistical analysis was performed for pTDP-43 pathology, since the pineal gland and SCN-related neurons of C9orf72 and nonC9orf72 cases do not show any pTDP-43 pathology. We neither performed statistical analysis for pathological assessments in the SON and PVN, since all cases were negative for poly(GA) and pTDP-43 pathology in the magnocellular cells of these brain nuclei
^c Three out of the six C9orf72 ALS and/or FTLD-TDP cases were not assessed for poly(GP), poly(GR) and poly(PR) pathology since prolonged fixation times of the pineal gland masked the detection of the aforementioned DPR inclusions
^d Pineal gland tissue of the nonC9orf72 ALS and/or FTLD-TDP and healthy control cases was only stained for the most abundant DPR (poly(GA)) to confirm the cases did not carry the C9orf72 repeat expansion
^e The general pathology in the hypothalamus was not semiquantitatively assessed
n.a. indicates not available; SCN, suprachiasmatic nucleus; SON, supraoptic nucleus; PVN, paraventricular nucleus; IQR, interquartile range; SD, standard deviation

Back to article page

ISSN: 2051-5960

Contact us

Submission enquiries: JJM.Hoozemans@vumc.nl
General enquiries: info@biomedcentral.com

Acta Neuropathologica Communications

Contact us