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- W2896370476 abstract "Neurogranin (Ng) is a postsynaptic protein that reflects synaptic degeneration in cerebrospinal fluid (CSF). We evaluated the specificity of Ng as a potential biomarker for Alzheimer's disease (AD) in a differential dementia diagnosis cohort enriched for cases with high total Tau (T-tau) concentrations. Additionally, Ng levels in human brain tissue were compared to those of CSF. Two independent cohorts were assessed for CSF Ng levels using ELISA (EUROIMMUN), one clinical and one autopsy cohort. The clinical cohort included 30 AD patients, 32 AD patients with high CSF T-tau levels (>1200 pg/ml), 12 patients with dementia other than AD, 13 patients with Creutzfeldt-Jakob disease (CJD) and 30 cognitively healthy controls. The autopsy-confirmed cohort included 50 AD patients, 48 patients with neurodegenerative diseases other than AD, and was compared to 50 cognitively healthy controls. In a subset of 16 autopsy-confirmed AD patients and 8 controls, Ng levels were measured in homogenized temporal and frontal cortex brain tissue using ELISA (EUROIMMUN). Analysis of variance and Pearson's correlations were performed on log-transformed Ng concentrations. The clinical cohort showed moderately elevated median Ng concentrations in AD (414 pg/ml) and non-AD patients (475 pg/ml) compared to controls (260 pg/ml) (both p<0.01), and even higher increases were observed in the AD high T-tau (857 pg/ml) and CJD (828 pg/ml) groups (both p<0.01 compared to controls, AD and non-AD). In the autopsy-confirmed cohort, there were no significant differences in CSF Ng levels between patients with AD (358 pg/ml), non-AD (275 pg/ml), and controls (259 pg/ml). Ng concentrations strongly correlated with T-tau and phosphorylated Tau-181 (P-tau181) in all groups (rho=0.5–0.9 for Ng and T-tau, and 0.6–0.9 for Ng and P-tau181), except for CJD patients in the clinical cohort. The Ng levels in brain tissue lysates did not correlate with CSF Ng levels in AD patients. Increased levels of Ng in CSF is not specific for AD, but strongly correlates with CSF T-tau and/or P-tau181, diminishing the added value of Ng for differential dementia diagnosis. Brain and CSF Ng levels are not correlated, which in combination with its relation to tau suggests that it is a general marker of synaptic dysfunction in neurodegenerative diseases." @default.
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- W2896370476 date "2018-07-01" @default.
- W2896370476 modified "2023-10-16" @default.
- W2896370476 title "P4‐270: NEUROGRANIN IN CEREBROSPINAL FLUID IS NOT SPECIFIC TO ALZHEIMER'S DISEASE DEMENTIA" @default.
- W2896370476 doi "https://doi.org/10.1016/j.jalz.2018.07.092" @default.
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