A Beta Levels In The Jugular Vein And High Molecular Weight A Beta Oligomer Levels In Csf Can Be Used As Biomarkers To Indicate The Anti-Amyloid Effect Of Ivig For Alzheimer'S Disease

Intravenous immunoglobulin (IVIg) has been a candidate as a potential anti-amyloid immunotherapy for Alzheimer disease (AD) because it contains anti-amyloid beta (A beta) antibodies. Although several studies with IVIg in AD have been published, changing levels of A beta efflux from the brain, or disaggregation of A beta species induced by immunotherapy, have not been properly investigated. Here, we carried out an open label study of therapy with IVIg in five patients with AD. We collected plasma from a peripheral vein (peripheral-plasma) and from the internal jugular vein (jugular-plasma) to estimate directly the efflux of soluble A beta from the brain. We also measured high molecular weight (HMW) A beta oligomers in CSF as a marker to detect disaggregated A beta. IVIg infusions were well tolerated in the majority of cases. However, one study subject had epileptic seizures after IVIg. Levels of HMW CSF A beta oligomers in all participants were significantly increased after IVIg. A beta 40 and A beta 42 levels in jugular-plasma were continuously or temporarily elevated after treatment in three of five patients who showed preserved cognitive function, whereas levels of those in peripheral- plasma did not correlate with reactivity to the treatment. Other conventional biomarkers including C-11-Pittsburgh compound B retention were not altered after the treatment. These findings imply that HMW A beta oligomer levels could be a better biomarker to reflect the anti-amyloid effects of IVIg than conventional A beta species; moreover, A beta in jugular-plasma seems to be a more direct and precise biomarker to estimate clearance of A beta from the brain rather than A beta in peripheral-plasma.