期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 53, 期 4, 页码 1523-1538出版社
IOS PRESS
DOI: 10.3233/JAD-160227
关键词
Alzheimer's disease; BACE1 protein; biomarkers; cerebrospinal fluid; ELISA; mild cognitive impairment; neurogranin; prognostic; ratio
资金
- University Research Fund of the University of Antwerp
- Institute Born-Bunge
- Alzheimer Research Foundation (SAO-FRA)
- Research Foundation - Flanders (FWO)
- Agency for Innovation by Science and Technology [IWT OO140105, IWT Baekeland 140262]
- Interuniversity Attraction Poles (IAP) program of the Belgian Science Policy Office
- Flanders Impulse Program on Networks for Dementia Research (VIND)
- EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant) [115372]
Background: In diagnosing Alzheimer's disease (AD), ratios of cerebrospinal fluid (CSF) biomarkers, such as CSF A beta(1-42)/tau, have an improved diagnostic performance compared to the single analytes, yet, still a limited value to predict cognitive decline. Since synaptic dysfunction/loss is closely linked to cognitive impairment, synaptic proteins are investigated as candidate CSF AD progression markers. Objective: We studied CSF levels of the postsynaptic protein neurogranin and protein BACE1, predominantly localized presynaptically, and their relation to CSF total-tau, A beta(1-42), A beta(1-40), and A beta(1-38). All six analytes were considered as single parameters as well as ratios. Methods: Every ELISA involved was based on monoclonal antibodies, including the BACE1 and neurogranin immunoassay. The latter specifically targets neurogranin C-terminally truncated at P75, a more abundant species of the protein in CSF. We studied patients with MCI due to AD (n = 38) and 50 dementia due to AD patients, as well as age-matched cognitively healthy elderly (n = 20). A significant subset of the patients was followed up by clinical and neuropsychological (MMSE) examinations for at least one year. Results: The single analytes showed statistically significant differences between the clinical groups, but the ratios of analytes indeed had a higher diagnostic performance. Furthermore, only the ratio of CSF neurogranin trunc P75/BACE1 was significantly correlated with the yearly decline in MMSE scores in patients with MCI and dementia due to AD, pointing toward the prognostic value of the ratio. Conclusion: This is the first study demonstrating that the CSF neurogranin trunc P75/BACE1 ratio, reflecting postsynaptic/presynaptic integrity, is related to cognitive decline.
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