Supplementary Table 1
Case / Age at death(yr) / Diagnosis / Disease duration
(yr) / Cause(s) of death / Post-mortem interval (hr)
MS1# / 42, F / MS (SP) / 12 / sepsis, bronchopneumonia / 24
MS2* / 44, F / MS (SP) / 10 / sepsis, bronchopneumonia / 9
MS3* / 55, F / MS (SP) / 32 / NA / 17
MS4* / 58, F / MS (SP) / 27 / sepsis, bronchopneumonia / 26
MS5* / 59, F / MS (SP) / 18 / NA / 20
MS6* / 59, M / MS (SP) / 23 / carcinomatosis (lung) / 15
MS7* / 62, M / MS (SP) / 24 / respiratory failure / 12
MS8* / 63, M / MS (SP) / 40 / sepsis, bronchopneumonia / 15
MS9* / 80, F / MS (SP) / 36 / bowel obstruction / 13
MS10* / 80, M / MS (SP) / 40 / carcinomatosis (lung) / 31
PD1# / 76, F / PD / 7 / sepsis, bronchopneumonia / 12
PD2# / 79, M / PD / 12 / sepsis, bronchopneumonia / 15
PD3# / 82, M / PD / NA / NA / 24
PD4# / 85, F / PD / 12 / respiratory failure / 17
PD5# / 87, M / PD / 19 / sepsis, infected sacral pressure sore / 15
AD1‡ / 72, M / AD / NA / cardiorespiratory failure / 12-24
AD2‡ / 73, F / AD / NA / sepsis, bronchopneumonia / 12-24
AD3‡ / 77, F / AD / NA / sepsis and urinary tract infection / 12-24
AD4‡ / 80, F / AD / NA / cardiac arrest / 12-24
AD5‡ / 86, M / AD / NA / cardiorespiratory failure / 12-24
CON1* / 39, F / - / - / sepsis, peritonitis / 9
CON2‡ / 40, M / - / - / ischaemic heart disease / 28
CON3* / 43, M / - / - / sepsis, urinary tract infection / 15
CON4* / 49, M / - / - / myocardial infarction / 11
CON5* / 60, M / - / - / cardiac arrest / 19
CON6* / 67, M / - / - / ischaemic heart disease / 18
CON7# / 68, M / - / - / carcinomatosis (colon) / 24
CON8* / 75, F / - / - / cardiac arrest / 7
CON9† / 96, F / - / - / sepsis, bronchopneumonia / 9
Supplementary Table 1. Clinical details of cases
The mean age of MS cases was 60.2 12.6, controls 59.7 18.9, PD 81.8 4.4 and AD 77.6 5.7. Kruskal-Wallis test showed a significant difference between groups (p=0.009). The age of MS and control cases were not significantly different, although PD and AD cases were significantly older than MS and controls (Mann Whitney U-test, p=0.027 and p=0.025). The difference in post-mortem intervals between MS, PD and controls was not statistically significant (Kruskal-Wallis test p=0.826). Furthermore, the percentage of respiratory enzyme deficient choroid plexus epithelial cells was not significantly different in cases where sepsis was a cause of death compared with cases without, when all cases with a neurological disease were pooled (sepsis versus non-sepsis: 2.83 ± 0.57 versus 2.96 ± 0.67, p=0.84) and controls (sepsis versus non-sepsis: 0.92 ± 0.23 versus 0.81 ± 0.19, p=0.81) were analysed separately).
*from NeuroResource (UK).#from UK Multiple Sclerosis and Parkinson’s Disease Tissue Bank.‡from Newcastle Brain Tissue Resource.†from Cleveland Clinic.AD; Alzheimer’s disease. CON; controls. MS; multiple sclerosis.PD; Parkinson’s disease.SP; secondary progressive.NA; not available.
Supplementary Table 2
AIF / rabbit polyclonal / apoptosis inducing factor / 1:100 / Cell Signalling Technologies
CD3 / mouse IgG1 / T lymphocytes / 1:400 / Dako
CD68 / mouse IgG1 / macrophages/
microglia / 1:400 / Dako
CD163 / mouse IgG1 / perivascular macrophages/
microglia / 1:300 / Novocastra
complex II-70kDa / mouse IgG1 / complex II subunit (nuclear DNA encoded) / 1:200 / Mitosciences
complex IV subunit-I / mouse IgG2a / complex IV subunit (mtDNA encoded) / 1:100 / Mitosciences
HLA-DR, DP, DQ / mouse IgG1 / MHC class II / 1:800 / Dako
iNOS / rabbit polyclonal / inducible nitric oxide synthase / 1:2500 / Millipore
MPO / rabbit polyclonal / myeloperoxidase / 1:4000 / Dako
NOX-1 / rabbit polyclonal / NADPH-oxidase subunit / 1:1000 / Sigma-Aldrich
p22phox / rabbit polyclonal / NADPH-oxidase subunit / 1:2000 / Santa Cruz Biotechnology
porin / mouse IgG2b / voltage gated anion channel / 1:400 / Mitosciences
Supplementary Table 2. Details of antibodies
MHC; major histocompatibility complex. NADPH; nicotinamide adenine dinucleotide phosphate
Supplementary Table 3
Complex IV deficient* / 173.4 75.9
(96) / 246.4 78.5
(91) / 229.4 84.9
(124) / 209.6 75.4
(162)
Complex IV intact / 117.5 28.1
(81) / 122.1 34.4
(52) / 105.8 23.6
(47) / 113.1 22.1
(71)
Supplementary Table 3. Area of choroid plexus epithelial cells in multiple sclerosis (MS), Parkinson’s disease (PD), Alzheimer’s disease (AD) and controls (CON)
Area of choroid plexus epithelial cells in m2. Parentheses indicate number of cells analyzed. Means standard deviation are shown. *The area of complex IV deficient cells in MS, PD, AD and controls were significantly greater than cells with intact complex IV activity (p<0.001).