Table 1.

Summary of clinical and biomarker data. Evaluation of the proband case and the affected sibling conducted over the last year (current age)

	Case I.3 (proband, woman)	Case I.1 (brother)
Age at onset	58 years	68 years
Symptoms at onset	1st delusions, 2nd memory	Memory
Current age	66 years	76 years
Neuropsychology
MMSE	16/30	23/30
Verbal fluency (1 min)	animals: 2; letter S: 2	animals: 7; letter S: 4
Boston Naming (15 items)	3/15 + 5 with phonetic clues	6/15 + 5 with phonetic clues
HVLT (12 items)	learning trials: 0-0-0 free recall: 0, cued: 0 recognition: 0	learning trials: 0-1-2 free recall: 0, cued: 0 recognition: 0
Clock Test	order 4/10, copy 6/10	order 2/10, copy 8/10
Functional status	GDS 5/CDR 2	GDS 3–4/CDR 1
CSF biomarkers (pg/ml) *
Aβ42	635	708
Aβ 40	11,391	14,403
Ratio Aβ42/40	0.056	0.049
T-tau	960	1037
P-tau	176	184
Erlangen score	4 (probable AD)	4 (probable AD)
ADAM10 55 kDa **	- 39%	- 69%
ADAM10 50 kDa **	- 34%	- 54%
ADAM10 80 kDa **	- 47%	- 26%
sAPPα 110 kDa#	- 73%	- 66%
sAPPα 120 kDa#	- 70%	- 63%
APOE genotype	3/3	2/3
Pattern of atrophy	Frontal + hippocampal	Diffuse cortical + hippocampal

CDR Clinical Dementia Rating scale (0 to 3), GDS Global Deterioration Scale (0 to 7), MMSE Mini-Mental State Examination, HVLT Hopkins Verbal Learning Test

*Cut-off points to consider the values consistent with AD are as follows: Aβ42 < 770 pg/ml; T-tau > 440 pg/ml; P-tau > 58 pg/ml; ratio Aβ42/40 < 0.068

** % Reduction of ADAM10 isoforms versus the mean for controls (shown in Fig. 2)

^#  % Reduction of sAPPα isoforms, compared to controls (Fig. 3)