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- Neely, G Gregory, et al.
(författare)
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A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha 2 delta 3 as an Evolutionarily Conserved Pain Gene
- 2010
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Ingår i: Cell. - : Elsevier Science B.V., Amsterdam.. - 0092-8674 .- 1097-4172. ; 143:4, s. 628-638
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Tidskriftsartikel (refereegranskat)abstract
- Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the alpha 2 delta family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (alpha 2 delta 3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, alpha 2 delta 3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in alpha 2 delta 3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in alpha 2 delta 3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.
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- van Rossum, Ineke A, et al.
(författare)
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Injury markers predict time to dementia in subjects with MCI and amyloid pathology.
- 2012
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Ingår i: Neurology. - 1526-632X. ; 79:17, s. 1809-16
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer disease (AD) can now be diagnosed in subjects with mild cognitive impairment (MCI) using biomarkers. However, little is known about the rate of decline in those subjects. In this cohort study, we aimed to assess the conversion rate to dementia and identify prognostic markers in subjects with MCI and evidence of amyloid pathology.
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- Vos, S. J. B., et al.
(författare)
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Prediction of Alzheimer disease in subjects with amnestic and nonamnestic MCI
- 2013
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 80:12, s. 1124-1132
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To compare the predictive accuracy of beta-amyloid (A beta)1-42 and total tau in CSF, Methods: We selected 399 subjects with aMCI and 226 subjects with naMCI from a multicenter Results: At least 1 follow-up was available for 538 subjects (86%). One hundred thirty-two subjects with Conclusions: AD biomarkers are useful to predict AD-type dementia in subjects with aMCI and naMCI.
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- Vos, S., et al.
(författare)
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Test sequence of CSF and MRI biomarkers for prediction of AD in subjects with MCI
- 2012
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 33:10, s. 2272-2281
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to identify the best diagnostic test sequence for predicting Alzheimer's disease (AD)-type dementia in subjects with mild cognitive impairment (MCI) using cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) biomarkers. We selected 153 subjects with mild cognitive impairment from a multicenter memory clinic-based cohort. We tested the CSF beta amyloid (A beta)1-42/tau ratio using enzyme-linked immunosorbent assay (ELISA) and hippocampal volumes (HCVs) using the atlas-based learning embeddings for atlas propagation (LEAP) method. Outcome measure was progression to AD-type dementia in 2 years. At follow-up, 48 (31%) subjects converted to AD-type dementia. In multivariable analyses, CSF A beta 1-42/tau and HCV predicted AD-type dementia regardless of apolipoprotein E (APOE) genotype and cognitive scores. Test sequence analyses showed that CSF A beta 1-42/tau increased predictive accuracy in subjects with normal HCV (p < 0.001) and abnormal HCV (p = 0.025). HCV increased predictive accuracy only in subjects with normal CSF A beta 1-42/tau (p = 0.014). Slope analyses for annual cognitive decline yielded similar results. For selection of subjects for a prodromal AD trial, the best balance between sample size and number of subjects needed to screen was obtained with CSF markers. These results provide further support for the use of CSF and magnetic resonance imaging biomarkers to identify prodromal AD. (c) 2012 Elsevier Inc. All rights reserved.
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