| 11. |
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| 12. |
- Glodzik-Sobanska, Lidia, et al.
(författare)
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The effects of normal aging and ApoE genotype on the levels of CSF biomarkers for Alzheimer's disease.
- 2009
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:5, s. 672-81
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Tidskriftsartikel (refereegranskat)abstract
- While cerebrospinal fluid (CSF) biomarkers are of use in the prediction and diagnosis of Alzheimer's disease our understanding of the background effects of age and the ApoE genotype is limited. Seventy-eight community-based normal volunteers (mean age 60+/-10 years, range 36-86) were examined to determine the relationships between CSF measures of total tau (T-tau), hyperphosphorylated tau (P-tau 231), amyloid beta (Abeta42/Abeta40 ratio), and isoprostane (IP) with age and ApoE genotype. The results showed that age by epsilon4 genotype interactions were found for P-tau231 (beta=1.82; p<0.05) and IP (beta=1.6; p<0.05). T-tau CSF concentration increased with age. The increasing CSF concentrations of P-tau and IP in epsilon4 carriers suggest that early tauopathy and oxidative stress may be related to the increased risk for AD. The data also suggest that T-tau changes are more age dependent than Abeta changes. The evidence that P-tau231 and IP are the earliest markers for the neuronal damage related to AD awaits longitudinal study.
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| 13. |
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| 14. |
- Hansson, Oskar, et al.
(författare)
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Combined rCBF and CSF biomarkers predict progression from mild cognitive impairment to Alzheimer's disease.
- 2009
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 30:2, s. 165-73
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to identify preclinical Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) using measurements of both regional cerebral blood flow (rCBF) and cerebrospinal fluid (CSF) biomarkers. Baseline rCBF assessments ((133)Xe method) were performed in 70 patients with MCI who were cognitively stable for 4-6 years, 69 patients with MCI who subsequently developed AD, and 33 healthy individuals. CSF was collected at baseline and analyzed for beta-amyloid(1-42), total tau and phophorylated tau. In contrast to patients with stable MCI, those who subsequently developed AD had decreased rCBF in the temporo-parietal cortex already at baseline. The relative risk of future progression to AD was particularly increased in MCI patients with decreased rCBF in parietal cortex (hazard ratio 3.1, P<0.0001). Subjects with pathological levels of both CSF tau and beta-amyloid(1-42) were also at high risk of developing AD (hazard ratio 13.4, P<0.0001). The MCI patients with a combination of decreased parietal rCBF and pathological CSF biomarkers at baseline had a substantially increased risk of future development of AD, with a hazard ratio of 24.3 (P<0.0001), when compared to those with normal CSF biomarkers. Moreover, decreased parietal rCBF (but not CSF biomarkers) was associated with a more rapid progression to AD. In conclusion, the combination of rCBF and CSF biomarkers improves the risk assessment of progression to AD in patients with MCI.
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| 16. |
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| 17. |
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| 18. |
- Janciauskiene, Sabina, et al.
(författare)
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A link between sICAM-1, ACE and parietal blood flow in the aging brain.
- 2009
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 30:9, s. 1504-1511
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Tidskriftsartikel (refereegranskat)abstract
- A connection between Alzheimer's disease (AD) and endothelium pathology has been inferred from measured decreases in both blood flow and metabolism in the parietal and temporal cortex. However, it is not known whether these alterations are seen in normal aging. We performed regional cerebral blood flow (rCBF) measurements in 22 AD patients and in 44 non-demented subjects during a simple test of information processing speed. Cerebrospinal fluid (CSF) levels of angiotensin-converting enzyme (ACE) and the soluble form of intercellular adhesion molecule-1 (sICAM-1) were analyzed in non-demented subjects. We found correlations between sICAM-1 and ACE (p=0.004), and sICAM (but not ACE) and CSF/plasma albumin ratio (p<0.0001). Higher concentrations of sICAM-1 (>893ng/L) and ACE (>5.22microg/L) were exclusively associated with lower parietal blood flow (p<0.001). The rCBF patterns in the AD and non-demented subjects with biomarker levels above median showed similar reductions in the temporoparietal areas. Our findings provide evidence that elevated CSF sICAM-1 and ACE are associated with lower perfusion levels in the parietal cortex of cognitively intact elderly.
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| 19. |
- Janovjak, Harald, et al.
(författare)
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Imaging and detecting molecular interactions of single transmembrane proteins
- 2006
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 27:4, s. 546-561
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Tidskriftsartikel (refereegranskat)abstract
- Single-molecule atomic force microscopy (AFM) provides novel ways to characterize structure-function relationships of native membrane proteins. High-resolution AFM-topographs allow observing substructures of single membrane proteins at sub-nanometer resolution as well as their conformational changes, oligomeric state, molecular dynamics and assembly. Complementary to AFM imaging, single-molecule force spectroscopy experiments allow detecting molecular interactions established within and between membrane proteins. The sensitivity of this method makes it possible to detect the interactions that stabilize secondary structures such as transmembrane alpha-helices, polypeptide loops and segments within. Changes in temperature or protein-protein assembly do not change the position of stable structural segments, but influence their stability established by collective molecular interactions. Such changes alter the probability of proteins to choose a certain unfolding pathway. Recent examples have elucidated unfolding and refolding pathways of membrane proteins as well as their energy landscapes. We review current and future potential of these approaches to reveal insights into membrane protein structure, function, and unfolding as we recognize that they could help answering key questions in the molecular basis of certain neuro-pathological dysfunctions.
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| 20. |
- Kadir, Ahmadul, et al.
(författare)
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PET imaging of the in vivo brain acetylcholinesterase activity and nicotine binding in galantamine-treated patients with AD
- 2008
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 29:8, s. 1204-1217
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Tidskriftsartikel (refereegranskat)abstract
- The effect of galantamine treatment on cortical acetylcholinesterase (AChE) activity and nicotinic receptor binding was investigated by positron emission tomography (PET) in 18 patients with mild Alzheimer's disease (AD) in relation to galantamine concentration and the patients’ cognitive performances. The first 3 months of the study was of a randomized double-blind placebo-controlled design, during which 12 patients received galantamine (16–24 mg/day) and 6 patients the placebo, and this was followed by 9 months’ galantamine treatment in all patients. The patients underwent PET examinations to measure cortical AChE activity (11C-PMP) and 11C-nicotine binding. Neuropsychological tests were performed throughout the study. Inhibition (30–40%) of cortical AChE activity was observed after 3 weeks to 12 months of galantamine treatment. No significant change in mean cortical 11C-nicotine binding was observed during the study. 11C-Nicotine binding, however, positively correlated with plasma galantamine concentration. Both the changes of AChE activity and 11C-nicotine binding correlated positively with the results of a cognitive test of attention. In conclusion, galantamine caused sustained AChE inhibition for up to 12 months. At the individual level, the in vivo cortical AChE inhibition and 11C-nicotine binding were associated with changes in the attention domain of cognition rather than episodic memory.
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