| 1. |
- Abramsson, Alexandra, 1973, et al.
(författare)
-
No Association of LOXL1 Gene Polymorphisms with Alzheimer's Disease
- 2011
-
Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 13:2, s. 160-166
-
Tidskriftsartikel (refereegranskat)abstract
- Aggregation of amyloid-beta is one of the major characteristics in brains of patients with Alzheimer's disease (AD). Although several mechanisms behind the formation of such aggregates have been suggested the regulatory factors are still unknown. The present study aimed at investigating the association of lysyl oxidase-like 1 (LOXL1) polymorphisms with AD diagnosis and cerebrospinal fluid biomarkers (CSF) for the disease. Proteins of the lysyl oxidase (LOX) family are involved in cross-linking extracellular matrix proteins to insoluble fibers and have been associated with neurodegenerative diseases including AD. Genetic polymorphisms in LOXL1 (rs1048661, rs3825942, and rs2165241) have been linked to exfoliation syndrome and exfoliation glaucoma, conditions that have shown association with AD. The polymorphisms were genotyped by Taqman allelic discrimination in a study sample including AD patients (n = 318) and controls (n = 575). In a subgroup of the population, the polymorphisms were analyzed in relation to APOE epsilon 4 genotype and to CSF (T-tau, P-tau, and A beta(1-42)). No evidence for associations of these polymorphisms with risk for AD or any of the studied CSF biomarkers measured was found. These results do not support LOXL1 as being a major risk gene for AD.
|
|
| 2. |
- Daborg, Jonny, et al.
(författare)
-
Complement Gene Single Nucleotide Polymorphisms and Biomarker Endophenotypes of Alzheimer's Disease
- 2013
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 35:1, s. 51-57
-
Tidskriftsartikel (refereegranskat)abstract
- The complement system has been implicated in both physiological synapse elimination and Alzheimer's disease (AD). Here, we investigated associations between four single nucleotide polymorphisms (SNPs) in complement genes and cerebrospinal fluid (CSF) biomarkers for AD in 452 neurochemically or neuropathologically verified AD cases and 678 cognitively normal controls. None of the SNPs associated with risk of AD but there were potential associations of rs9332739 in the C2 gene and rs4151667 in the complement factor B gene with CSF tau levels (p = 0.023) and Mini-Mental State Examination scores (p = 0.012), both of which may be considered markers of disease intensity/severity.
|
|
| 3. |
- Anckarsäter, Rolf, 1956, et al.
(författare)
-
Association between thyroid hormone levels and monoaminergic neurotransmission during surgery.
- 2007
-
Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 32:8-10, s. 1138-43
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human studies assessing thyroid hormone metabolism in relation to brain monoaminergic activity in vivo are scarce. The few studies that do exist suggest significant associations between thyroid function and monoaminergic activity, but the cause-and-effect relationships are far from elucidated. METHODS: We simultaneously collected cerebrospinal fluid (CSF) and serum samples from 35 patients undergoing orthopaedic surgery before, 3h after and the morning after interventions and performed analyses for thyroid hormones and monoamine metabolites. RESULTS: At baseline, the CSF 3-methoxy-4-hydroxyphenylglycol concentrations were significantly correlated to the serum T(3)/T(4) ratio (rho=0.41, p=0.017). During surgery, serum thyroid hormones and the T(3)/T(4) ratio decreased (p<0.0001), while the CSF T(3)/T(4) ratio increased (p=0.0009). There were no correlations between serum and CSF levels of T(3) and T(4) at any of the samplings. Strong correlations were noted between baseline CSF thyroid hormone concentrations and subsequent increases in CSF 5-hydroxyindoleacetic acid (5-HIAA), and homovanillinic acid (HVA), but not vice versa. CONCLUSIONS: Thyroid hormone levels in serum and CSF during stress seem to be distinctly regulated. Baseline thyroid hormone activity may facilitate changes in brain monoaminergic neurotransmission in response to stress.
|
|
| 4. |
- Anckarsäter, Rolf, 1956, et al.
(författare)
-
Cerebrospinal fluid protein reactions during non-neurological surgery.
- 2007
-
Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 115:4, s. 254-9
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study changes in cerebrospinal fluid (CSF) protein markers of blood-CSF barrier integrity and immunological reactions during surgical stress. SUBJECTS AND METHODS: Thirty-five patients without neurological or psychiatric disorders undergoing knee replacements had CSF and serum samples drawn from spinal and arterial catheters before, 3 h after and the morning after surgery. RESULTS: Serum albumin decreased during surgery and CSF albumin decreased during and after surgery, and, as a consequence, the CSF/serum albumin ratio decreased significantly during the study period, especially after the intervention. In contrast, CSF concentrations of beta-2-microglobuline (beta2M) increased significantly during surgery and remained high. The CSF general marker beta-trace protein (betaTP) remained unchanged. CONCLUSIONS: Central nervous system protein reactions to a non-neurological surgical intervention include sharply decreased permeability of albumin into the CSF and signs of intrathecal inflammatory activity.
|
|
| 5. |
- Anckarsäter, Rolf, 1956, et al.
(författare)
-
Non-neurological surgery results in a neurochemical stress response.
- 2008
-
Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 115:3, s. 397-9
-
Tidskriftsartikel (refereegranskat)abstract
- There is a paucity of studies assessing changes in measures of human neurotransmission during stressful events, such as surgery. Thirty-five patients without any neurological disorders undergoing knee replacements with spinal bupivacaine anaesthesia and propofol sedation had cerebrospinal fluid (CSF) drawn from a spinal catheter before, three hours after and the morning after surgery. The CSF concentrations of the dopamine metabolite homovanillinic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), which are related to the activity of the dopaminergic and serotonergic systems of the brain, increased sharply during surgery and reached 188% and 166% of their initial concentrations on the morning after the intervention (p < 0.0001). The CSF concentrations of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglucol (MHPG) increased modestly (non-significantly) during and after surgery. The HVA/5-HIAA ratios initially increased but returned to the initial level during the night after surgery. We conclude that non-neurological surgery, in this case to the lower limb, is accompanied by a marked central nervous stress response in spite of a spinal blockade.
|
|
| 6. |
- Andersson, Carl-Henrik, et al.
(författare)
-
A Genetic Variant of the Sortilin 1 Gene is Associated with Reduced Risk of Alzheimer's Disease
- 2016
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 53:4, s. 1353-1363
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a neurodegenerative disorder represented by the accumulation of intracellular tau protein and extracellular deposits of amyloid-β (Aβ) in the brain. The gene sortilin 1 (SORT1) has previously been associated with cardiovascular disease in gene association studies. It has also been proposed to be involved in AD pathogenesis through facilitating Aβ clearance by binding apoE/Aβ complexes prior to cellular uptake. However, the neuropathological role of SORT1 in AD is not fully understood. To evaluate the associations between gene variants of SORT1 and risk of AD, we performed genetic analyses in a Swedish case-control cohort. Ten single nucleotide polymorphisms (SNPs), covering the whole SORT1 gene, were selected and genotyped in 620 AD patients and 1107 controls. The SNP rs17646665, located in a non-coding region of the SORT1 gene, remained significantly associated with decreased risk of AD after multiple testing (pc = 0.0061). In addition, other SNPs were found to be nominally associated with risk of AD, as well as altered cognitive function and the CSF biomarker Aβ42, but these associations did not survive correction for multiple testing. The fact that SORT1 has been strongly associated with risk of cardiovascular disease is intriguing as cardiovascular disease is also regarded as a risk factor for AD. Finally, increased knowledge about SORT1 function has a potential to increase our understanding of APOE, the strongest risk factor for AD.
|
|
| 7. |
|
|
| 8. |
- Brinkmalm-Westman, Ann, 1966, et al.
(författare)
-
SNAP-25 is a promising novel cerebrospinal fluid biomarker for synapse degeneration in Alzheimer's disease
- 2014
-
Ingår i: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Synaptic degeneration is an early pathogenic event in Alzheimer's disease, associated with cognitive impairment and disease progression. Cerebrospinal fluid biomarkers reflecting synaptic integrity would be highly valuable tools to monitor synaptic degeneration directly in patients. We previously showed that synaptic proteins such as synaptotagmin and synaptosomal-associated protein 25 (SNAP-25) could be detected in pooled samples of cerebrospinal fluid, however these assays were not sensitive enough for individual samples. Results: We report a new strategy to study synaptic pathology by using affinity purification and mass spectrometry to measure the levels of the presynaptic protein SNAP-25 in cerebrospinal fluid. By applying this novel affinity mass spectrometry strategy on three separate cohorts of patients, the value of SNAP-25 as a cerebrospinal fluid biomarker for synaptic integrity in Alzheimer's disease was assessed for the first time. We found significantly higher levels of cerebrospinal fluid SNAP-25 fragments in Alzheimer's disease, even in the very early stages, in three separate cohorts. Cerebrospinal fluid SNAP-25 differentiated Alzheimer's disease from controls with area under the curve of 0.901 (P < 0.0001). Conclusions: We developed a sensitive method to analyze SNAP-25 levels in individual CSF samples that to our knowledge was not possible previously. Our results support the notion that synaptic biomarkers may be important tools for early diagnosis, assessment of disease progression, and to monitor drug effects in treatment trials.
|
|
| 9. |
- Bromander, Sara, et al.
(författare)
-
Cerebrospinal fluid insulin during non-neurological surgery.
- 2010
-
Ingår i: J Neural Transm (Vienna, Austria:1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 20, s. 328-329
-
Tidskriftsartikel (refereegranskat)abstract
- Insulin plays an important metabolic and transmitter role in the central nervous system, but few studies have investigated the relationship between central and peripheral insulin concentrations. 35 patients undergoing knee surgery had cerebrospinal fluid (CSF) samples drawn before, 3 h after, and in the morning following surgery. Serum insulin concentrations increased after surgery and CSF insulin concentrations changed in the same direction with far smaller amplitude. These results indicate that the blood-brain barrier protects the brain from stress-induced peripheral hormonal fluctuations.
|
|
| 10. |
|
|
