| 1. |
- Zetterberg, Henrik, 1973, et al.
(författare)
-
Intra-individual stability of CSF biomarkers for Alzheimer's disease over two years
- 2007
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1387-2877. ; 12:3, s. 255-60
-
Tidskriftsartikel (refereegranskat)abstract
- This study examines the intra-individual stability of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) over 2 years in 83 patients with mild cognitive impairment (MCI) and 17 cognitively healthy control individuals. All participants underwent clinical and neuropsychological evaluation and lumbar puncture at baseline and after 2 years at a university hospital memory clinic. CSF was analyzed for total tau (T-tau), phospho-tau(181) (P-tau(181)) and amyloid-beta(1-42) (Abeta(1-42)). During the 2-year observational time, 12 MCI patients progressed to AD and 3 progressed to vascular dementia, while 68 remained stable. Baseline T-tau and P-tau(181) levels were elevated in the MCI-AD group as compared to the stable MCI patients and the control group (p<0.01), while baseline Abeta(1-42) levels were lower (p<0.001). Stable MCI patients were biochemically indistinguishable from controls. The biomarker levels at baseline and after 2 years showed Pearson R values between 0.81 and 0.91 (p<0.001) and coefficients of variation of 7.2 to 8.7%. In conclusion, intra-individual biomarker levels are remarkably stable over 2 years. Thus, even minor biochemical changes induced by treatment against AD should be detectable using these biomarkers, which bodes well for their usefulness as surrogate markers for drug efficacy in clinical trials.
|
|
| 2. |
- Lättman, Håkan, et al.
(författare)
-
At what age becomes Cliostomum corrugatum adult?
- 2006
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The objective was to investigate at what the age specimen of Cliostomum corrugatum become fertile in order to estimate the time span between the meiosis events. The species has its main distribution in Europe but has also been found on the west coast of British Columbia and is red listed, e.g., in Sweden (nearly threatened), Denmark, Germany and England. In the province of Östergötland, southern Sweden it is most frequent on old Quercus robur trees in open oak forest or meadows. I may also be found on other deciduous trees as Ulmus and Fraxinus species. It is mainly groving on the flat terminal parts of the rough bark of the tree trunks and not on the sides of the cracks. Cliostomum corrugatum does not grow on young oak trees. The smallest tree trunk diameter with Cliostomum corrugatum was is 0.65 m, a tree of at least 100 years of age. On two localities in Östergötland all oaks were studied and the size of the trees and the size of the largest thallus of Cliostomum corrugatum were recorded. Out of this data the size of how small a tree can possibly be for hosting Cliostomum corrugatum. This estimate was compared with the size of the smallest thalli with apothecia and the size of trees on which these appeared. With knowledge of the peripheral secondary growth of oaks it was possible to estimate the age of the youngest fertile Cliostomum corrugatum to about 30 years. Thus, equal to the time span between two meiosis events.
|
|
| 3. |
- Lättman, Håkan, et al.
(författare)
-
Generation time estimated to be 25-30 years in Cliostomum cossugatum (Ach.) Fr.
- 2009
-
Ingår i: The Lichenologist. - : Britich Lichen Society. - 0024-2829 .- 1096-1135. ; 41:5, s. 557-559
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge of spore to spore generation time is extremely important for several reasons. As it is the shortest generation time, it indicates the maximum nucleotide substitution rate over time and provides a rate limit for the evolution of a species. In population genetics most calculations involving time use ‘generations’ as the unit of measurement and in order to convert these ‘generations’ into ‘years’, knowledge of generation time is needed but rarely available. Knowledge of generation time may also be essential for conservation purposes and assessments of migration history. This knowledge also makes it possible to estimate both the age of a population and also to determine to what extent a population represents the genetic diversity of a species (Rosenberg & Nordborg 2002). In this paper we present a method for assessing generation length for lichens using Cliostomum corrugatum (Ach.) Fr. as an example. This lichen was selected for investigation because it is restricted to forests with long temporal continuity (Lättman et al. 2009) and information on generation time is essential to estimate the rate of dispersal at the landscape level.
|
|
| 4. |
|
|
| 5. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Cerebrospinal fluid concentrations of peptides derived from chromogranin B and secretogranin II are decreased in multiple sclerosis
- 2007
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 103:5, s. 1932-1939
-
Tidskriftsartikel (refereegranskat)abstract
- Novel biomarkers for multiple sclerosis (MS) could improve diagnosis and provide clues to pathogenesis. In this study surface-enhanced laser desorption/ionization time-of-flight mass spectrometry was used to analyze protein expression in CSF from 46 MS patients, 46 healthy siblings to the patients, and 50 unrelated healthy controls. Twenty-four proteins in the mass range 2–10 kDa were expressed at significantly different levels (p < 0.01) in a robust manner when comparing the three groups. Identities of three proteins were determined using biochemical purification followed by tandem mass spectrometric analysis. Immunoprecipitation experiments confirmed the identities for two peptides derived from chromogranin B (m/z 6252) and from secretogranin II (m/z 3679). These peptides were all decreased in MS when compared with siblings or controls. Radioimmunoassays specific for each peptide confirmed these differences. The lowered concentrations did not correlate to the axonal damage marker neurofilament light protein and may thus reflect functional changes rather than neurodegeneration. Further studies will investigate the involvement of these peptides in MS pathogenesis.
|
|
| 6. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment.
- 2009
-
Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 302:4, s. 385-93
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Small single-center studies have shown that cerebrospinal fluid (CSF) biomarkers may be useful to identify incipient Alzheimer disease (AD) in patients with mild cognitive impairment (MCI), but large-scale multicenter studies have not been conducted. OBJECTIVE: To determine the diagnostic accuracy of CSF beta-amyloid(1-42) (Abeta42), total tau protein (T-tau), and tau phosphorylated at position threonine 181 (P-tau) for predicting incipient AD in patients with MCI. DESIGN, SETTING, AND PARTICIPANTS: The study had 2 parts: a cross-sectional study involving patients with AD and controls to identify cut points, followed by a prospective cohort study involving patients with MCI, conducted 1990-2007. A total of 750 individuals with MCI, 529 with AD, and 304 controls were recruited by 12 centers in Europe and the United States. Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative likelihood ratios (LRs) of CSF Abeta42, T-tau, and P-tau for identifying incipient AD. RESULTS: During follow-up, 271 participants with MCI were diagnosed with AD and 59 with other dementias. The Abeta42 assay in particular had considerable intersite variability. Patients who developed AD had lower median Abeta42 (356; range, 96-1075 ng/L) and higher P-tau (81; range, 15-183 ng/L) and T-tau (582; range, 83-2174 ng/L) levels than MCI patients who did not develop AD during follow-up (579; range, 121-1420 ng/L for Abeta42; 53; range, 15-163 ng/L for P-tau; and 294; range, 31-2483 ng/L for T-tau, P < .001). The area under the receiver operating characteristic curve was 0.78 (95% confidence interval [CI], 0.75-0.82) for Abeta42, 0.76 (95% CI, 0.72-0.80) for P-tau, and 0.79 (95% CI, 0.76-0.83) for T-tau. Cut-offs with sensitivity set to 85% were defined in the AD and control groups and tested in the MCI group, where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83% (95% CI, 78%-88%), specificity 72% (95% CI, 68%-76%), positive LR, 3.0 (95% CI, 2.5-3.4), and negative LR, 0.24 (95% CI, 0.21-0.28). The positive predictive value was 62% and the negative predictive value was 88%. CONCLUSIONS: This multicenter study found that CSF Abeta42, T-tau, and P-tau identify incipient AD with good accuracy, but less accurately than reported from single-center studies. Intersite assay variability highlights a need for standardization of analytical techniques and clinical procedures.
|
|
| 7. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
CSF biomarkers: pinpointing Alzheimer pathogenesis.
- 2009
-
Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1180, s. 28-35
-
Forskningsöversikt (refereegranskat)abstract
- Intense research during the last decades has resulted in an unprecedented accumulation of knowledge regarding the pathogenesis of Alzheimer's disease. Primarily, the focus has been directed toward amyloid and tau pathology and their relations to synaptic and neuronal loss. However, as the complexity of the disease becomes increasingly evident, the importance of other factors, such as inflammation, oxidative stress, and mitochondrial dysfunction, grow apparent. Here, we review available CSF biomarkers for these pathological processes. We also consider their usability in clinical practice and in clinical trials.
|
|
| 8. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Elevated cerebrospinal fluid F2-isoprostane levels indicating oxidative stress in healthy siblings of multiple sclerosis patients.
- 2007
-
Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 414:3, s. 233-6
-
Tidskriftsartikel (refereegranskat)abstract
- Lipid peroxidation has been implicated in the pathogenesis of multiple sclerosis (MS). Isoprostanes, isomers of prostaglandins, are produced by free radical-mediated peroxidation of fatty acids in vivo and can be quantified in biological fluids. This study examines the levels of cerebrospinal fluid (CSF) F2-isoprostanes (F2-iPs) in MS patients (n=46), their healthy siblings (n=46) and unrelated controls (n=50). The median CSF F2-iP concentration (range) was significantly higher in siblings of MS patients, as compared to healthy controls (40.0 [7.1-68.7] and 29.1 [6.4-60.3] pg/mL, respectively, p=0.031). MS patients demonstrated F2-iP levels intermediate between siblings and controls. F2-iP levels in MS patients and siblings correlated significantly (R=0.360, p=0.012). These results suggest that siblings of MS patients have an increased oxidative stress response to environmental and/or genetic factors that may be involved in MS pathogenesis.
|
|
| 9. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Elevated cerebrospinal fluid levels of prostaglandin E2 and 15-(S)-hydroxyeicosatetraenoic acid in multiple sclerosis.
- 2009
-
Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 265:4, s. 459-64
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To test the hypothesis that the arachodinic acid metabolites prostaglandin E2 (PGE2) and 15-(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in cerebrospinal fluid (CSF) are elevated and reflect neuroinflammation and degenerative changes in multiple sclerosis (MS). PATIENTS AND METHODS: We measured PGE2 and 15(S)-HETE concentrations, as well as markers of axonal and astroglial injury in CSF from 46 MS patients, 46 healthy siblings and 50 controls. RESULTS: We found elevated levels of both PGE2 and 15(S)-HETE in MS compared with the control and sibling groups. Siblings had lower PGE2 levels and higher 15(S)-HETE levels than controls. There were no correlations between either PGE2 or 15(S)-HETE and clinical scores of MS severity or biochemical markers of axonal or astroglial injury. CONCLUSION: These data suggest no direct involvement of PGE2 and 15(S)-HETE in the MS disease process. Rather, the elevated levels reflect a general up-regulation of arachidonic acid metabolism and neuroinflammation.
|
|
| 10. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Future screening for incipient Alzheimer's disease--the influence of prevalence on test performance.
- 2009
-
Ingår i: European neurology. - : S. Karger AG. - 1421-9913 .- 0014-3022. ; 62:4, s. 200-3
-
Forskningsöversikt (refereegranskat)abstract
- Much effort has been made to identify and verify diagnostic biomarkers for early stage Alzheimer's disease (AD). The need for this is often advocated by possible future disease-modifying treatments, likely to be most effective if initiated early in the disease process. Since the neurodegenerative process probably starts many years before the first onset of symptoms, such future drugs are likely to invoke a need for screening presymptomatic individuals. Here, we speculate on the performance of currently available AD biomarkers in hypothetical screening programs of different designs. We note that many diagnostic tests will have an excellent ability to exclude upcoming AD. However, even the best tests will suffer from poor positive predictive values given the relatively low disease prevalence in populations with no or very few symptomatic individuals, also when taking future converters to AD into account. The magnitude of this problem, which is common among most screening programs, will depend on the efficacy, safety and cost of the future anti-AD drugs. A number of tentative solutions to the problem, apart from better tests, are discussed.
|
|
