A function for CysC in these situations is supported by changes in cystatin C (CysC) expression and secretion levels in the brain associated with a variety of neurological illnesses and in animal models of neurodegeneration. Alzheimer's disease risk is elevated by a variation in the CysC gene (CST3) (AD). The pathogenesis of AD is characterised by neurodegeneration, neurofibrillary tangles made primarily of hyperphosphorylated tau, and the deposition of oligomeric and fibrillar forms of Amyloid (A) in the walls of the cerebral artery and neuropil. CysC's co-localization with A in amyloid-laden vascular walls and in senile plaque cores of amyloid in the brains of patients with AD, Down's syndrome, Hereditary Cerebral Haemorrhage With Amyloidosis, Dutch Type (HCHWAD), and cerebral infarction initially raised questions about its potential role in the disease. CysC's co-localization with A in amyloid-laden vascular walls and in senile plaque cores of amyloid in the brains of patients with AD, Down's syndrome, Hereditary Cerebral Haemorrhage With Amyloidosis, Dutch Type (HCHWA-D), and cerebral infarction initially raised questions about its potential role in the disease. In the brains of elderly people without dementia, CysC also co-localizes with an amyloid deposit. There is a wealth of evidence indicating that CysC functions as a protective factor in AD. Studies conducted in vitro have demonstrated that CysC binds to A and prevents A from oligomerizing and forming fibrils. Results obtained in vivo from the brains and plasma of transgenic mice that deposit A supported CysC's connection with the soluble, non-pathological form of A and its inhibitory effect on the development of A plaques. The connection of CysC with A was also discovered in the brain and Cerebrospinal Fluid (CSF) of AD patients and non-demented controls. Furthermore, in vitro studies have shown that CysC protects neuronal cells from a variety of toxins that can cause cell death, such as oligomeric and fibrillar A. According to these studies, decreased CysC levels associated with AD may enhance neuronal susceptibility and diminish their capacity to stop neurodegeneration. This review elaborates on CysC's neuroprotective functions in AD and the therapeutic utility of this protein in clinical settings.
