Mapping the genetic landscape of early-onset Alzheimer’s disease in a cohort of 36 families

Mol, Merel O.; van der Lee, Sven J.; Hulsman, Marc; Pijnenburg, Yolande A. L.; Scheltens, Phillip; Seelaar, Harro; van Swieten, John C.; Kaat, Laura Donker; Holstege, Henne; van Rooij, Jeroen G. J.

doi:10.1186/s13195-022-01018-3

Alzheimer's Research & Therapy

Table 1 Summary of the clinical characteristics and genetic findings of the 36 families evaluated in this study

From: Mapping the genetic landscape of early-onset Alzheimer’s disease in a cohort of 36 families

Family ID	Patients (n)	Age at onset (average)	Clinical diagnoses	Family history - other relatives	PV	VUS	APOE-risk*	PRS*	Summary (genetics)
1	2	57.0	AD	Unknown	APP		0.24	−0.49	PV
2	2	48.0	AD	Dementia NOS	GRN		0.24	0.61	PV, PRS
3	2	69.5	AD	EOAD	PSEN1		0.01	−0.26	PV
4	2	56.0	AD	EOAD	PSEN1		−0.36	−0.08	PV
5	2	64.5	AD	EOAD	PSEN1		−0.36	−0.33	PV
6	2	49.0	AD	EOAD	PSEN1		0.84	0.06	PV
7	2	59.0	AD	EOAD	PSEN1		0.24	−0.23	PV
8	2	57.5	AD	EOAD	SORL1		1.44	0.47	PV, APOE, PRS
9	2	65.0	AD, MCI	EOAD		ABCA7	2.04	0.20	VUS, APOE
10	2	64.0	AD	Dementia NOS		BIN1	1.44	0.02	VUS, APOE
11	2	69.5	AD, MCI	Dementia NOS		CR1	1.44	0.37	VUS, APOE
12	2	69.5	AD	EOAD		FERMT2	2.04	0.20	VUS, APOE
13	2	69.0	AD	Dementia NOS, PD		MADD	2.04	−0.02	VUS, APOE
14	2	63.0	AD	Dementia NOS		PRNP	0.24	0.12	VUS
15	2	59.5	AD	EOAD		SORL1	1.44	0.15	VUS, APOE
16	2	73.0	AD	EOAD		SQSTM1	0.84	0.42	VUS
17	2	68.0	AD	Dementia NOS			1.44	0.60	APOE, PRS
18	4	70.3	AD	Dementia NOS			2.04	0.56	APOE, PRS
19	2	62.5	AD, FTD	Dementia NOS			1.44	−0.17	APOE
20	2	68.5	AD	ALS			1.44	−0.14	APOE
21	2	62.0	AD	Dementia NOS, PSY			2.04	0.32	APOE
22	2	56.0	AD, MCI	AD, FTD			2.04	−0.15	APOE
23	2	65.0	AD	Dementia NOS			1.44	−0.04	APOE
24	2	68.0	AD, MCI	LOAD			1.44	−0.08	APOE
25	3	56.7	AD, CAA, MCI	EOAD			1.64	0.41	APOE
26	3	59.0	AD, MCI	EOAD			1.24	−0.30	APOE
27	2	59.0	AD, FTD	Dementia NOS			2.04	0.01	APOE
28	2	67.5	AD	EOAD, PD			−0.36	−0.18	Risk factors unknown
29	3	63.5	AD	Dementia NOS			0.44	−0.33	Risk factors unknown
30	2	64.9	AD	Unknown			−0.36	−0.10	Risk factors unknown
31	2	73.0	AD	Dementia NOS			0.84	−0.01	Risk factors unknown
32	2	63.5	AD, MCI	Dementia NOS			−0.36	−0.19	Risk factors unknown
33	2	63.5	AD	LOAD			0.84	0.19	Risk factors unknown
34	2	59.5	AD, MCI	Dementia NOS, PSY			0.24	0.04	Risk factors unknown
35	2	69.0	AD	Dementia NOS			0.24	−0.15	Risk factors unknown
36	2	59.0	AD	Dementia NOS			0.84	0.19	Risk factors unknown
Total	77
Average		63.1					0.96	3.50

In four families (12, 18, 19, and 30), an unaffected relative was included for segregation analysis. Data on these individuals, as well as all individual patients, are provided in Table S3. *APOE-risk and PRS indicate the increased AD risk for each family based on APOE and PRS effect sizes, respectively, after scaling to the mean of an in-house population dataset (n = 980). Abbreviations: ALS, amyotrophic lateral sclerosis; AD, Alzheimer’s disease; CAA, cerebral amyloid angiopathy; Dementia NOS, dementia not otherwise specified; EOAD, early-onset AD; FTD, frontotemporal dementia; LOAD, late-onset AD; MCI, mild cognitive impairment; PD, Parkinson’s disease; PSY, psychiatric disorder; PV, pathogenic variant; VUS, variant of uncertain significance

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ISSN: 1758-9193

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