Alterations of CSF Cystatin C Levels and Their Correlations with CSF Αβ40 and Αβ42 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-β (Αβ) 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 Αβ aggregation, induction of autophagy and induction of cell division. CysC levels may be altered and may have a potential link with cerebrospinal fluid (CSF) Aβ 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 Aβ40 and Aβ42 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 Aβ levels. We found that in comparison to the normal control group, both CSF CysC and CSF Aβ42 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 Aβ40 and Aβ42 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 Aβ metabolism and suggest that modulation of the CysC level in the brain might produce a disease-modifying effect in dementia with characteristic amyloid deposits.

Dementia risk in renal dysfunction

“…A recent study demonstrated the presence of low CSF levels of cystatin C in patients with AD in comparison with healthy controls. 58 Although serum levels of cystatin C are presumably more related to renal dysfunction and CSF levels of cystatin C more to AD pathology, it is difficult to establish a one-to-one relationship due to intercorrelations.…”

Neuropsychiatric Features of Neurosyphilis: Frequency, Relationship with the Severity of Cognitive Impairment and Comparison with Alzheimer Disease

“…Previous studies have found that CSF tau levels were increased in neurosyphilis versus controls [21] or that they were unchanged [22]. CSF levels of Aβ (1-42), which are believed to represent amyloid plaque pathology, were decreased in the atrophic form of general paresis [12,22]. Although neurosyphilis encompasses AD-like cognitive impairment [11] and AD-like decreases in CSF Aβ (1-42) [12], we found discrepancies in neuropsychiatric syndromes between neurosyphilis and AD.…”

“…Wang et al [11] showed a similar pattern of cognitive impairments in memory, language, and executive function between patients with neurosyphilis-dementia and patients with mild AD. Biologically, patients with AD and those with neurosyphilis-dementia appear to share decreased Aβ42 in the cerebral spinal fluid (CSF) [12]. Whether patients with neurosyphilis also share an AD-like pattern of neuropsychiatric symptoms is unknown.…”

Promoting Autophagic Clearance: Viable Therapeutic Targets in Alzheimer's Disease

“…Genetic deletion of cystatin B and C has been shown to improve neurological deficits and restore autophagic dysfunction in the TgCRND8 and hAPP-J20 mouse models of AD [127,213]. However, conflicting reports indicate that cystatin C is neuroprotective in several neurodegenerative diseases, and these effects may be mediated by inducing autophagy [214][215][216][217]. Future studies should examine the effects of cystatins in AD [218], and whether neuroprotection is attenuated in the absence of autophagy.…”