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- Eckerström, Carl, et al.
(author)
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Combination of Hippocampal Volume and Cerebrospinal Fluid Biomarkers Improves Predictive Value in Mild Cognitive Impairment.
- 2010
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In: Dementia and Geriatric Cognitive Disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 29:4, s. 294-300
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Journal article (peer-reviewed)abstract
- Background: Mild cognitive impairment (MCI) is a heterogeneous condition, and the prognosis differs within the group. Recent findings suggest that hippocampal volumetry and CSF biomarkers can be used to predict which MCI patients have an underlying neurodegenerative disorder. Objective: To examine the combined predictive value of hippocampal volume and CSF levels of total tau (T-tau) and beta-amyloid(42) (Abeta(42)) in stable and converting MCI patients. The participants (n = 68) included patients with MCI at baseline and who converted to dementia by the time of the 2-year follow-up (n = 21), stable MCI patients (n = 21) and healthy controls (n = 26). Methods: The Göteborg MCI study is a clinically based longitudinal study with biannual clinical assessments. Hippocampal volumetry was performed manually, based on data from the 0.5-tesla MRI investigations at baseline. Baseline CSF levels of T-tau and Abeta(42) were measured using commercially available, enzyme-linked immunosorbent assays. Results: The converting MCI group had significantly smaller left hippocampi, lower CSF Abeta(42) and higher T-tau compared to both the stable MCI group and the healthy controls. Multivariate analysis revealed that a combination of the variables outperformed the prognostic ability of the separate variables. Conclusions: Hippocampal volumes supplement the prognostic accuracy of CSF Abeta(42) and T-tau in MCI.
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| 2. |
- Mattsson, Niklas, 1979, et al.
(author)
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Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain
- 2010
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In: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 20:4, s. 1039-1048
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Journal article (peer-reviewed)abstract
- Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50), and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sA beta PP and A beta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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