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].sub.40 and A[beta].sub.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 .sup.11 C-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.