I have been interested in clusterin for some time, as it is somewhat similar to ApoE in several ways. Clusterin is produced at high levels in the brain by astrocytes (like ApoE), It occurs in HDL-like particles in the brain (like ApoE), and it strongly increases amyloid formation and neurite toxicity in APP transgenic mice (DeMattos et al., 2002).

In this paper by the Breteler group, clusterin was found to be increased by about 10 percent in the plasma of AD patients compared to controls in this population-based study. There were not many AD cases studied for clusterin levels (only 60), though there were large numbers of non-AD cases. Plasma clusterin was found to be increased with increasing AD severity. These are interesting findings, though the changes are somewhat small.

I am also aware of unpublished studies comparing plasma clusterin in AD and control plasma which so far have not found differences between the groups. However, these studies are not in epidemiologically ascertained sample sets.

So, while the paper...  Read more

I have been interested in clusterin for some time, as it is somewhat similar to ApoE in several ways. Clusterin is produced at high levels in the brain by astrocytes (like ApoE), It occurs in HDL-like particles in the brain (like ApoE), and it strongly increases amyloid formation and neurite toxicity in APP transgenic mice (DeMattos et al., 2002).

In this paper by the Breteler group, clusterin was found to be increased by about 10 percent in the plasma of AD patients compared to controls in this population-based study. There were not many AD cases studied for clusterin levels (only 60), though there were large numbers of non-AD cases. Plasma clusterin was found to be increased with increasing AD severity. These are interesting findings, though the changes are somewhat small.

I am also aware of unpublished studies comparing plasma clusterin in AD and control plasma which so far have not found differences between the groups. However, these studies are not in epidemiologically ascertained sample sets.

So, while the paper from the Breteler group is interesting, it would be useful to see if this is replicable in other sample sets.

View all comments by David Holtzman

Using Rules-Based Medicine techniques and samples from a large population-based cohort, the authors show that clusterin levels in plasma are slightly elevated in Alzheimer's disease and also in other dementia forms as compared to non-demented individuals. They also demonstrate that this change is downstream of the dementia phenotype and not related to its pathogenesis. This result is similar to what has been seen, for example, for α1-antichymotrypsin and some other inflammatory markers, and provides information of limited diagnostic value.

View all comments by Henrik Zetterberg