Alterations of CSF cystatin C levels and their correlations with CSF Αß40 and Αß42 levels in patients with Alzheimer's disease, dementia with lewy bodies and the atrophic form of general paresis.

ABSTRACT

Immunohistochemical studies have revealed that cystatin C (CysC) co-localizes with amyloid-ß (Αß) in amyloid-laden vascular walls and in the senile plaque cores of amyloid. In vitro and in vivo animal studies suggest that CysC protects against neurodegeneration by inhibition of cysteine proteases, inhibition of Αß aggregation, induction of autophagy and induction of cell division. CysC levels may be altered and may have a potential link with cerebrospinal fluid (CSF) Aß levels in various types of dementia with characteristic amyloid deposits, such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and the atrophic form of general paresis (AF-GP). We assessed the serum and CSF levels of CysC and the CSF levels of Aß40 and Aß42 in patients with AD (n = 51), DLB (n = 26) and AF-GP (n = 43) and normal controls (n = 30). Using these samples, we explored the correlation between CSF CysC and CSF Aß levels. We found that in comparison to the normal control group, both CSF CysC and CSF Aß42 levels were significantly lower in all three dementia groups (all p<0.001); serum CysC levels were the same in the AD and DLB groups, and were lower in the AF-GP group (p = 0.008). The CSF CysC levels were positively correlated with both the CSF Aß40 and Aß42 levels in the AD, AF-GP and normal control groups (r = 0.306∼0.657, all p<0.05). Lower CSF CysC levels might be a common feature in dementia with characteristic amyloid deposits. Our results provide evidence for the potential role of CysC involvement in Aß metabolism and suggest that modulation of the CysC level in the brain might produce a disease-modifying effect in dementia with characteristic amyloid deposits.