| 61. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
It is all about clearance.
- 2011
-
Ingår i: Biomarkers in medicine. - 1752-0363. ; 5:2
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 62. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Lessons from Multicenter Studies on CSF Biomarkers for Alzheimer's Disease.
- 2010
-
Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2010
-
Forskningsöversikt (refereegranskat)abstract
- Several single-center studies have confirmed the usability of cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer's disease (AD), even in early disease stages. Large scale multicenter studies have principally confirmed this, although such studies have also indicated the presence of significant intercenter and interlaboratory variations in biomarker measurements. Such variations may hamper the development of biomarkers and their introduction into clinical routine practice. Recently a quality control program run by the Alzheimer's Association was started in order to harmonize procedures of laboratories world-wide. This program provides both standardized guide lines and external control CSF samples, and will allow longitudinal evaluation of laboratory performance.
|
|
| 63. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism.
- 2010
-
Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 10:51
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The metabolism of amyloid precursor protein (APP) and beta-amyloid (Abeta) is widely studied in Alzheimer's disease, where Abeta deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid metabolism in patients with Lyme neuroborreliosis (LNB). METHODS: The first part of the study was a cross-sectional cohort study in 61 patients with acute facial palsy (19 with LNB and 42 with idiopathic facial paresis, Bell's palsy) and 22 healthy controls. CSF was analysed for the beta-amyloid peptides Abeta38, Abeta40 and Abeta42, and the amyloid precursor protein (APP) isoforms alpha-sAPP and beta-sAPP. CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage. The second part of the study was a prospective cohort-study in 26 LNB patients undergoing consecutive lumbar punctures before and after antibiotic treatment to study time-dependent dynamics of the biomarkers. RESULTS: In the cross-sectional study, LNB patients had lower levels of CSF alpha-sAPP, beta-sAPP and P-tau, and higher levels of CSF NFL than healthy controls and patients with Bell's palsy. In the prospective study, LNB patients had low levels of CSF alpha-sAPP, beta-sAPP and P-tau at baseline, which all increased towards normal at follow-up. CONCLUSIONS: Amyloid metabolism is altered in LNB. CSF levels of alpha-sAPP, beta-sAPP and P-tau are decreased in acute infection and increase after treatment. In combination with earlier findings in multiple sclerosis, cerebral SLE and HIV with cerebral engagement, this points to an influence of neuroinflammation on amyloid metabolism.
|
|
| 64. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
- 2011
-
Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4, s. 386-395.e6
-
Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
|
|
| 65. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
To know or not to know: ethical issues related to early diagnosis of Alzheimer's disease.
- 2010
-
Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2010
-
Forskningsöversikt (refereegranskat)abstract
- In Alzheimer's disease (AD), pathological processes start in the brain long before clinical dementia. Biomarkers reflecting brain alterations may therefore indicate disease at an early stage, enabling early diagnosis. This raises several ethical questions and the potential benefits of early diagnosis must be weighted against possible disadvantages. Currently, there are few strong arguments favouring early diagnosis, due to the lack of disease modifying therapy. Also, available diagnostic methods risk erroneous classifications, with potentially grave consequences. However, a possible benefit of early diagnosis even without disease modifying therapy is that it may enable early decision making when patients still have full decision competence, avoiding problems of hypothetical consents. It may also help identifying patients with cognitive dysfunction secondary to other diseases that may be responsive to treatment already today.
|
|
| 66. |
|
|
| 67. |
- Mollenhauer, B., et al.
(författare)
-
Diagnosis and biomarkers: CSF
- 2010
-
Ingår i: Neuropsychiatric and Cognitive Changes in Parkinson's Disease and Related Movement Disorders: Diagnosis and Management. - Cambridge : Cambridge University Press. - 9781139856669 ; , s. 97-108
-
Bokkapitel (refereegranskat)abstract
- n the last two decades, the elucidation of the molecular pathology of several neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), has resulted in new biomarkers that have increased our knowledge on distinct and shared pathologies, as well as temporal dynamics in the appearance of pathology, in neurodegenerative diseases. This knowledge has resulted in new thoughts on neuropreventive strategies and how to monitor the pharmacodynamic effects of such treatments. Commencing with the finding of extracellular secretion of β-amyloid (Aβ) in 1992, followed by numerous validation studies, the analysis of Aβ fragments 1-42 (Aβ1-42) in cerebrospinal fluid (CSF) in combination with total and/or phosphorylated tau protein was recently (together with neuroimaging methods) included in research criteria for the clinical diagnosis of the most frequent dementia disorder, AD [1]. Along similar lines, the Alzheimer’s Association and the National Institute on Aging of the National Institutes of Health have worked on new diagnostic criteria and guidelines for AD, which were published in April 2011 [2]. These guidelines postulate three clinically relevant stages of the disease, with a continuum between and within each stage. The first stage is a preclinical phase, which might last a decade or more. In this phase there is evidence of abnormal biomarker patterns, such as low CSF Aβ1-42 levels and/or increased amyloid tracer retention on positron emission tomography (PET) of the brain, but without signs of cognitive impairment [3]. The second stage is designated mild cognitive impairment due to AD [4].
|
|
| 68. |
- Mulugeta, Ezra, et al.
(författare)
-
Cerebrospinal Fluid Levels of sAPPα and sAPPβ in Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates.
- 2011
-
Ingår i: International journal of Alzheimer's disease. - : Hindawi Limited. - 2090-0252. ; 2011
-
Tidskriftsartikel (refereegranskat)abstract
- We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPα sAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPα and sAPPβ levels between the groups. Significant correlations were observed between sAPPα and sAPPβ and between sAPPβ and Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPα and sAPPβ levels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPα correlated with p-Tau and sAPPβ with Aβ40. The differential association between sAPPα and sAPPβ with Aβ and Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD.
|
|
| 69. |
- Mulugeta, Ezra, et al.
(författare)
-
CSF amyloid {beta}38 as a novel diagnostic marker for dementia with Lewy bodies.
- 2011
-
Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 82:2, s. 160-4
-
Tidskriftsartikel (refereegranskat)abstract
- Background The clinical distinction between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) is sometimes difficult, particularly in mild cases. Although CSF markers such as amyloid β42 (Aβ42) and P-tau can distinguish between AD and normal controls, their ability to distinguish between AD and DLB is not adequate. Objective This study aims to investigate whether CSF markers, in particular levels of Aβ38, can differentiate between mild AD and DLB. Methods 85 individuals were included after standardised diagnostic procedures: 30 diagnosed as probable AD, 23 probable DLB, 20 probable Parkinson's disease dementia and 12 non-demented control subjects. CSF levels of Aβ38, Aβ40 and Aβ42 were determined using commercially available ultra-sensitive multi-array kit assay (MSD) for human Aβ peptides. Total tau (T-tau) and phosphorylated tau (P-tau) were analysed using ELISA (Innotest). In addition, combinations (Aβ42/Aβ38, Aβ42/Aβ40, Aβ42/P-tau and Aβ42/Aβ38/P-tau) were assessed. Results Significant between group differences were found for all CSF measures, and all except Aβ40, Aβ42 and Aβ42/P-tau differed between AD and DLB. The Aβ42/Aβ38 ratio was the measure that best discriminated between AD and DLB (AUC 0.765; p<0.005), with a sensitivity of 78% and a specificity of 67%. Conclusion This study suggests that the level of Aβ38 can potentially contribute in the diagnostic distinction between AD and DLB when combined with Aβ42. Single measures had low diagnostic accuracy, suggesting that developing a panel of markers is the most promising strategy. Studies with independent and larger samples and a priori cut-offs are needed to test this hypothesis.
|
|
| 70. |
- Mustafiz, Tamanna, et al.
(författare)
-
Characterization of the brain β-amyloid isoform pattern at different ages of Tg2576 mice.
- 2011
-
Ingår i: Neuro-degenerative diseases. - : S. Karger AG. - 1660-2862 .- 1660-2854. ; 8:5, s. 352-63
-
Tidskriftsartikel (refereegranskat)abstract
- Although genetic and biochemical studies have suggested a cardinal role for β-amyloid (Aβ) in Alzheimer's disease, the underlying mechanism(s) of how Aβ induces neurodegeneration is still unclear. Our objective was to investigate the consequences of Aβ, especially on tau phosphorylation at specific epitopes important for Alzheimer's disease.
|
|
