| 1. |
|
|
| 2. |
- Höglund, Kina, 1976, et al.
(författare)
-
Effect of statins on beta-amyloid metabolism in humans: potential importance for the development of senile plaques in Alzheimer's disease.
- 2006
-
Ingår i: Acta neurologica Scandinavica. Supplementum. - : Hindawi Limited. - 0065-1427 .- 0001-6314 .- 1600-0404. ; 185, s. 87-92
-
Tidskriftsartikel (refereegranskat)abstract
- According to the amyloid cascade hypothesis, both familial and sporadic Alzheimer's disease (AD) is caused by the toxic effect of over-production and/or aggregation of beta-amyloid (Abeta). Recent cell and animal studies have linked the production of Abeta to high levels of cholesterol and the use of statins, compounds inhibiting the de novo synthesis of cholesterol. Epidemiological studies have also supported such linkage by showing a reduced prevalence of AD for subjects taking statins. A limited number of clinical studies have been published trying to elucidate the effect of statin treatment on amyloid precursor protein (APP) processing and metabolism of brain cholesterol in AD in humans and this review focuses on the current state of these clinical studies. The results are contradictory, but the overall interpretation suggests that statin treatment probably does not have a direct impact through lowering of cholesterol on the APP processing and Abeta production in humans. To confirm this, further clinical studies needs to be performed with extended treatment periods and where several parameters (lipid profile, lipoproteins, sterols, biomarkers related to AD and APP metabolites) are analyzed, both in the cerebrospinal fluid and plasma. The pleiotropic effects of statins should be investigated further. One approach is presented in this review.
|
|
| 3. |
- Portelius, Erik, 1977, et al.
(författare)
-
An Alzheimer's disease-specific beta-amyloid fragment signature in cerebrospinal fluid.
- 2006
-
Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 409:3, s. 215-9
-
Tidskriftsartikel (refereegranskat)abstract
- Pathogenic events in Alzheimer's disease (AD) involve an imbalance between the production and clearance of the neurotoxic beta-amyloid peptide (Abeta), especially the 42 amino acid peptide Abeta1-42. While much is known about the production of Abeta1-42, many questions remain about how the peptide is degraded. To investigate the degradation pattern, we developed a method based on immunoprecipitation combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry that determines the Abeta degradation fragment pattern in cerebrospinal fluid (CSF). We found in total 18 C-terminally and 2 N-terminally truncated Abeta peptides and preliminary data indicated that there were differences in the detected Abeta relative abundance pattern between AD and healthy controls. Here, we provide direct evidence that an Abeta fragment signature consisting of Abeta1-16, Abeta1-33, Abeta1-39, and Abeta1-42 in CSF distinguishes sporadic AD patients from non-demented controls with an overall accuracy of 86%.
|
|
| 4. |
- Wallin, Anders, 1950, et al.
(författare)
-
CSF biomarkers for Alzheimer's Disease: levels of beta-amyloid, tau, phosphorylated tau relate to clinical symptoms and survival
- 2006
-
Ingår i: Dement Geriatr Cogn Disord. - : S. Karger AG. ; 21:3, s. 131-138
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) samples from 21 patients with a clinical diagnosis of Alzheimer's disease (AD) participating in a 5-year treatment study with the choline esterase inhibitor tacrin were retrospectively analyzed for the contents of beta-amyloid (Abeta42), total tau (T-tau) and phosphorylated tau (P-tau). A significant positive correlation between the level of P-tau and the number of symptoms according to the DSM-IV criteria (p = 0.041) and the NINCDS-ADRDA (p = 0.029) was observed (i.e. higher levels were found in cases with more symptoms). A significant positive correlation between T-tau, P-tau and ADAS-cog score was identified (i.e. higher levels were found with more severe cognitive dysfunction). Patients who died during the 5-year follow-up had significantly lower levels of Abeta42 (p = 0.011) than those who were still alive. Patients who had died in a 6-year follow-up had significantly lower levels of Abeta42 (p = 0.034) and higher levels of T-tau (p = 0.041) than patients still alive. CONCLUSION: CSF biomarkers do aid the clinical diagnosis of AD. Increased levels of P-tau and T-tau are possible markers for severity and abundance of symptoms in AD. Low levels of Abeta42 may indicate a higher risk of early death in AD.
|
|
| 5. |
- Zetterberg, Henrik, 1973, et al.
(författare)
-
Neurochemical aftermath of amateur boxing
- 2006
-
Ingår i: ARCHIVES OF NEUROLOGY. - : American Medical Association (AMA). - 0003-9942. ; 63:9, s. 1277-1280
-
Tidskriftsartikel (refereegranskat)
|
|
