11 General introduction Table 1. Current and predicted incidence of neuroinflammatory diseases Disease (Proposed) Aetiology Innate immune response involvement Adaptive immune response involvement Incidence % or number/ 100000 Predicted change in prevalence Ref MS Autoimmune Viral Microglial and macrophage activation, ↑ROS, complement, ↑innate receptors, ↑cytokines, ↑chemokines ↑HSPs ↑neurotrophins Antibodies / T cells to CNS antigens. 9.64 ↑2.4% per year 6,7 AD, other dementias AD – misfolded and aggregated tau and Abeta Activated and dystrophic microglia, ↑TNF-α, ↑IFN-γ, ↑chemokines, ↑complement, ↑TLRs ↑antibody and T-cell response 9.33% ↑3.3% per year (triple by 2050) 1,3,7 PD Loss of dopaminergic neurons in SN due to α-syn-inclusions ↑TLRs, ↑CD14, activated NK cells, microglial activation, ↑IL-1β, ↑IL-6, ↑TNF-α ↑T-cells ↑antibody response 100-200 double in 25 years 7-9 HD Expansion of CAG (Q) in huntingtin gene induces aberrant toxic protein ↑microglial proliferation, ↑complement, not reported 0.02-9.71 ↑15-20% per decade 7,10 SMA SMN1 gene mutations ↑IL-6, ↑IL-1β not reported 1-2 not reported 7,11 ALS (MND) Aberrant aggregated proteins due to mutations SOD1, TDP; C9orf72 or FUS genes ↑complement, ↑CD14, ↑macrophages, ↑IL-6, ↑TNF-α ↑CD4+ ↑CD8+ T-cells 1.9 ↑69% in 25 years 7,11, 12 Prion diseases Infectious forms of misfolded aggregated forms of prion protein ↑microglial activation, ↑IL-1β, ↑IL-6, ↑complement, ↑ROS, mast cells expressing PrP B cells aid transport of PrP variable not reported 7 Stroke Ischemia or Haemorrhage ↑lymphopenia, ↑NK cells, ↑IL-10 ↑Th2 responses 115 ↑44% in 20 years 13,14 TBI Open and head Injury, Deceleration Injuries, Chemical/Toxic, Hypoxia, Tumors, ↑pro-inflammatory cytokines, ↑TLRs ↑T-cells ↑B-cells 295 not reported 7,15 HIV/AIDS HIV encephalopathy, toxoplasmosis, PML ↓IL-27, ↓IFN-γ, ↓CD4 cells, ↑IL-4 ↓T-cells, immunesenescence 0.8% depending on country 16 Meningitis Bacterial and viral infections ↑IL-6, ↑TNF-α, ↑NK cells, ↑microglial activation ↑T-cells ↑B-cells 0.2-1000 outbreak dependent 17,18 Ageing Natural event ↑proinflammatory cytokines, ↓NK cell function ↓T-cells n/a n/a 19 Epilepsy Unprovoked seizures, febrile events, autoantibodies ↑proinflammatory cytokines, ↑chemokines, ↑TLRs, ↑complement ↑autoantibodies T and B-cell activation 45-81.7 ↑ 20-22
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