Patients with sporadic FTLD exhibit similar increases in lysosomal proteins and storage material as patients with FTD due to GRN mutations

Davis, Skylar E.; Cook, Anna K.; Hall, Justin A.; Voskobiynyk, Yuliya; Carullo, Nancy V.; Boyle, Nicholas R.; Hakim, Ahmad R.; Anderson, Kristian M.; Hobdy, Kierra P.; Pugh, Derian A.; Murchison, Charles F.; McMeekin, Laura J.; Simmons, Micah; Margolies, Katherine A.; Cowell, Rita M.; Nana, Alissa L.; Spina, Salvatore; Grinberg, Lea T.; Miller, Bruce L.; Seeley, William W.; Arrant, Andrew E.

doi:10.1186/s40478-023-01571-4

Table 1 Description of patients

From: Patients with sporadic FTLD exhibit similar increases in lysosomal proteins and storage material as patients with FTD due to GRN mutations

#	Group	GRN Mutation*	Sex	Age at death	Clinical diagnosis**	Primary neuropath diagnosis***	PMI (h)
1	Ctrl	n/a	F	81	MCI, amnestic	Braak 2	30.3
2	Ctrl	n/a	M	77	MCI, executive	AGD	4.9
3	Ctrl	n/a	F	86	Control	CVD; AGD	7.8
4	Ctrl	n/a	M	76	Control	Braak 2, limbic AGD	8.2
5	Ctrl	n/a	F	86	Control	iLBD, brainstem predominant	6.4
6	GRN	c.1145del:p.Thr382Serfs*30	M	74	nfvPPA/CBS	FTLD-TDP-A	30.9
7^#	GRN	c.347C > A:p.Ser116*	M	68	bvFTD	FTLD-TDP-A	13.5
8	GRN	c.264 + 2 T > C	F	73	nfvPPA/CBS	FTLD-TDP-A	20.7
9	GRN	c.1477C > T:p.Arg493*	F	66	bvFTD	FTLD-TDP-A	7.4
10	GRN	c.709-2A > G	M	64	bvFTD	FTLD-TDP-A	7.2
11	GRN	c.1256_1263dup:p.Ile422Glufs*72	M	66	DLB	LBD, FTLD-TDP-A	10.1
12	GRN	c.1A > T:p.Met1?	F	59	CBS	FTLD-TDP-A	9.5
13	GRN	c.1477C > T:p.Arg493*	F	70	PPA, unspecified	FTLD-TDP-A	9.1
14	GRN	c.1216C > T:p.Gln406*	F	56	bvFTD	FTLD-TDP-A	7.6
15	GRN	c.349 + 1G > A	F	78	mixed FTD	FTLD-TDP-A	19
16	GRN	c.328C > T:p.Arg110*	F	66	bvFTD	FTLD-TDP-A	17.1
17	GRN	c.708 + 1G > A	F	64	CBS	FTLD-TDP-A	10.5
18	GRN	c.1256_1263dup:p.Ile422Glufs*72	M	72	AD-type dementia	AD, FTLD-TDP-A	7.2
19	TDP-A	n/a	F	78	nfvPPA	FTLD-TDP-A	9
20	TDP-A	n/a	F	66	CBS	FTLD-TDP-A	17.3
21	TDP-A	n/a^†	M	72	PPA-mixed	FTLD-TDP-A	23.8
22	TDP-A	n/a	M	63	CBS	FTLD-TDP-A	15.7
23	TDP-A	n/a	M	70	bvFTD	FTLD-TDP-A	8.5
24	TDP-A	n/a	F	73	bvFTD	FTLD-TDP-A	7.4
25	TDP-A	n/a	F	78	AD-type dementia vs. FTD	FTLD-TDP-A	8.1
26	TDP-C	n/a	F	69	svPPA	FTLD-TDP-C	10.7
27	TDP-C	n/a	M	66	svPPA	FTLD-TDP-C	10
28	TDP-C	n/a	F	68	svPPA	FTLD-TDP-C	8.4
29	TDP-C	n/a	M	66	svPPA	FTLD-TDP-C	14.5
30	TDP-C	n/a	M	75	svPPA	FTLD-TDP-C	3.8
31	TDP-C	n/a	F	75	svPPA	FTLD-TDP-C	7.9
32	TDP-C	n/a	F	71	svPPA	FTLD-TDP-C	13
33	Pick's	n/a	M	64	CBS	Pick's Disease	13.7
34	Pick's	n/a	F	78	nfvPPA	Pick's Disease	14.5
35	Pick's	n/a	F	67	AD-type dementia	Pick's Disease	6.8
36	Pick's	n/a	F	63	nfvPPA	Pick's Disease	4.3
37	Pick's	n/a	M	57	bvFTD	Pick's Disease	12.4
38	Pick's	n/a	F	73	nfvPPA	Pick's Disease	9.6
39	Pick's	n/a	M	78	svPPA	Pick's Disease	7.5

*All GRN mutations were heterozygous. **Disease considered most likely to explain the clinical syndrome. ***No control subject had limbic TDP-43 proteinopathy. ^#case 7 was only analyzed for lysosomal storage markers in fixed tissue. ^†case 21 was negative for pathogenic GRN mutations, but had intronic GRN variants of unknown significance. PMI postmortem interval, AD Alzheimer’s disease, AGD argyrophilic grain disease, bvFTD behavioral variant frontotemporal dementia, CBS corticobasal syndrome, DLB dementia with Lewy bodies, LBD Lewy body disease, MCI mild cognitive impairment, nfvPPA nonfluent variant primary progressive aphasia, svPPA semantic variant primary progressive aphasia

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