ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics

Table 1 Demographic details and causes of death of CADASIL and other subjects

Parameter	Controls (Age-matched)	CADASIL	Old Controls	SVD‖
n (total = 55)	11	16	10	10
Mean age (years)	57.5	59.0	83.4	81.0
Range (years)	49–69	33–74	78–94	67–96
Gender (M/F)	6/5	10/6	2/8	5/5
Mean age at onset (years)	-	46.9	-	n/a
Duration of Disease (years)	-	12.6	-	n/a
Key disease features	.	Migraine, TIA, lacunar strokes, cognitive impairment	-	White matter disease, lacunar strokes, dementia
NOTCH3 Mutations	-	Arg133Cys (6); Arg141Cys (2); Arg153Cys (2); Arg169Cys (3); Cys445Arg (1); Arg558Cys (1); Arg985Cys (1)	-	-
Cause(s) of death	Cardiac arrest, cancer, renal failure, infection	Bronchopneumonia, heart failure	Heart failure, cancer, ischemic bowel infection.	Heart failure, Cancer, GI bleed, sudden death
Neuropathological Features
Braak stage	0	0	0-IV	1–4
CERAD score	1	0	2	0–2
Median Vascular Pathology score /10	3	9	5.5	6
Mean Sclerotic Index	0.28	0.36	0.27	0.30

Mean age of controls or young controls (YC) was not different to CADASIL and the mean age of the old controls (OC) was not different from SVD group. Mean age of OC group was different to YC and CADASIL (P < 0.05). No significant cerebrovascular or neurodegenerative disease pathology. Pathological findings not consistent with any neurological or psychiatric disease. The post-mortem interval between death and immersion fixation of tissue ranged 9–96 h. The length of fixation of tissues prior to paraffin embedding ranged 1 to 7 months. ‖In most of the subsequent quantitative analysis as indicated we used SVD cases (n = 8). Sclerotic index: *P < 0.05, different to YC; **P < 0.05, different to all groups. ANOVA and post-hoc analysis, †P < 0.41, CADASIL different from YC, old controls (OC) and PADMAL; ††P = 0.000, all groups; ‡P < 0.002, CADASIL was different to all groups, except PADMAL, but PADMAL was different to OC and SVD; ‡‡P = 0.000, CADASIL was different to all groups, except COL4A1, but COL4A1 was different to OC. Abbreviations: CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CERAD, Consortium to Establish a Registry for Alzheimer’s Disease; GI, gastrointestinal; SVD, small vessel disease; PADMAL, pontine autosomal dominant microangiopathy with leukoencephalopathy (caused by collagen IV A1 UTR mutation in hereditary multi-infarct dementia of Swedish type); TIA, transient ischaemic attack

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