| 1. |
- Andreasen, N, et al.
(författare)
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Cerebrospinal fluid tau and Abeta42 as predictors of development of Alzheimer's disease in patients with mild cognitive impairment
- 1999
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Ingår i: Neuroscience Letters. - 0304-3940. ; 273:1, s. 5-8
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Tidskriftsartikel (refereegranskat)abstract
- We studied CSF-tau and CSF-Abeta42 in 16 patients with mild cognitive impairment (MCI) who at follow-up investigations 6-27 months later had progressed to Alzheimer's disease (AD) with dementia. For comparison, we studied 15 age-matched healthy individuals. At baseline, 14/16 (88%) of MCI patients had high CSF-tau and/or low CSF-Abeta42 levels. These findings show that these CSF-markers are abnormal before the onset of clinical dementia and that they may help to identify MCI patients that will develop AD. This is especially important when drugs with potential effects on the progression of AD will reach the clinical phase.
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| 2. |
- Andreasen, N, et al.
(författare)
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Evaluation of CSF-tau and CSF-Abeta42 as diagnostic markers for Alzheimer disease in clinical practice
- 2001
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Ingår i: Archives of Neurology. - 0003-9942. ; 58:3, s. 373-379
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the diagnostic potential of cerebrospinal fluid (CSF) levels of tau and beta-amyloid protein ending at amino acid 42 (Abeta42) as biomarkers for Alzheimer disease (AD) in clinical practice. DESIGN: A 1-year prospective study. SETTING: Community population-based sample of all consecutive patients admitted for investigation of cognitive symptoms to the Pitea River Valley Hospital, Pitea, Sweden. PATIENTS: A total of 241 patients with probable AD (n = 105), possible AD (n = 58), vascular dementia (n = 23), mild cognitive impairment (n = 20), Lewy body dementia (n = 9), other neurological disorders (n = 3), and psychiatric disorders (n = 5) and nondemented individuals (n = 18). MAIN OUTCOME MEASURES: Cerebrospinal fluid tau and CSF-Abeta42 were assayed each week as routine clinical neurochemical analyses. Sensitivity and specificity were defined using the regression line from 100 control subjects from a multicenter study. Positive and negative predictive values were calculated for different prevalence rates of AD. RESULTS: We found increased CSF-tau and decreased CSF-Abeta42 levels in probable and possible AD. Sensitivity was 94% for probable AD, 88% for possible AD, and 75% for mild cognitive impairment, whereas specificity was 100% for psychiatric disorders and 89% for nondemented. Specificity was lower in Lewy body dementia (67%) mainly because of low CSF-Abeta42 levels and in vascular dementia (48%) mainly because of high CSF-tau levels. Sensitivity for CSF-tau and CSF-Abeta42 increased in patients with AD possessing the ApoE epsilon4 allele, approaching 100%. At a prevalence of AD of 45%, the positive predictive value was 90% and the negative predictive value was 95%. CONCLUSIONS: Cerebrospinal fluid tau and CSF-Abeta42 have so far been studied in research settings, under conditions providing data on the optimal performance. We examined a prospective patient sample, with assays run in clinical routine, giving figures closer to the true performance of CSF-tau and CSF-Abeta42. The predictive value for AD was greater than 90%. Therefore, these biomarkers may have a role in the clinical workup of patients with cognitive impairment, especially to differentiate early AD from normal aging and psychiatric disorders.
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| 3. |
- Andreasen, N, et al.
(författare)
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Sensitivity, specificity, and stability of CSF-tau in AD in a community-based patient sample
- 1999
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Ingår i: Neurology. - 1526-632X. ; 53:7, s. 1488-1488
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the sensitivity and specificity of CSF-tau in clinical practice as a diagnostic marker for AD compared with normal aging and depression, to study the stability of CSF-tau in longitudinal samples, and to determine whether CSF-tau levels are influenced by different covariates such as gender, age, duration or severity of disease, or possession of the APOE-epsilon4 allele. METHODS: Consecutive AD patients from a community-based sample were studied, including 407 patients with AD (274 with probable AD and 133 with possible AD), 28 patients with depression, and 65 healthy elderly control subjects. A follow-up lumbar puncture was performed in 192 AD patients after approximately 1 year. CSF-tau was determined using a sandwich ELISA, which was run as a routine clinical neurochemical analysis. RESULTS: CSF-tau was increased in probable (690+/-341 pg/mL; p < 0.0001) and possible (661+/-447 pg/mL; p < 0.0001) AD, but not in depression (231+/-110 pg/mL) compared with control subjects (227+/-101 pg/mL). Receiver operating characteristics analysis showed that a cutoff level of 302 pg/mL resulted in a sensitivity of 93% (95% CI, 90-96%) and a specificity of 86% (95% CI, 75-94%), with an area under the curve of 0.95 to discriminate AD from control subjects. Within the AD group, CSF-tau did not differ significantly between baseline and follow-up investigations, and was relatively stable between baseline and 1-year follow-up levels, with a coefficient of variation of 21.0%. High CSF-tau levels were also found in most AD patients with very short duration of dementia, and with Mini-Mental State Examination scores >23 (n = 205). In total, 193 of 205 patients (sensitivity, 94%) had a CSF-tau level higher than 302 pg/mL. CONCLUSIONS: CSF-tau has a high sensitivity and specificity to differentiate AD from normal aging and depression, as demonstrated in a large community-based series of consecutive AD patients during which analyses were run continually in a clinical neurochemical laboratory. The increase in CSF-tau is found very early in the disease process in AD, is stable over time, and has a low interindividual variation on repeated sampling. Although high CSF-tau is found in some neurologic conditions (e.g., stroke), these findings suggest that CSF-tau may be of use to help in differentiating AD from normal aging and depression, especially early in the course of the disease, when the symptoms are vague and the diagnosis is especially difficult.
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| 4. |
- Blennow, K., et al.
(författare)
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EVOLUTION OF A beta 42 AND A beta 40 LEVELS AND A beta 42/A beta 40 RATIO IN PLASMA DURING PROGRESSION OF ALZHEIMER'S DISEASE: A MULTICENTER ASSESSMENT
- 2009
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Ingår i: Journal Of Nutrition Health & Aging. - 1279-7707. ; 13:3, s. 205-208
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Konferensbidrag (refereegranskat)abstract
- Objective: To better understand the seemingly contradictory plasma beta-amyloid (A beta) results in Alzheimer's disease (AD) patients by using a newly developed plasma A beta assay, the INNO-BIA plasma A beta forms, in a multicenter study. Methods: A combined retrospective analysis of plasma A beta isoforms on mild cognitive impairment (MCI) from three large cross-sectional studies involving 643 samples from the participating German and Swedish centers. Results: Detection modules based on two different amino (N)-terminal specific A beta monoclonal antibodies demonstrated that A beta in plasma could be reliable quantified using a sandwich immunoassay technology with high precision, even for low A beta 42 plasma concentrations. A beta 40 and A beta 42 concentrations varied consistently with the ApoE genotype, while the A beta 42/A beta 40 ratio did not. Irrespective of the decrease of the A beta 42/A beta 40 ratio with age and MMSE, this parameter was strongly associated with AD, as defined in this study by elevated hyperphosphorylated (P-tau181P) levels in cerebrospinal fluid (CSF). Conclusion: A highly robust assay for repeatedly measuring A beta forms in plasma such as INNO-BIA plasma A beta forms might be a useful tool in a future risk assessment of AD.
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| 5. |
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| 6. |
- Davidsson, P, et al.
(författare)
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Differential increase in cerebrospinal fluid-acetylcholinesterase after treatment with acetylcholinesterase inhibitors in patients with Alzheimer's disease
- 2001
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Ingår i: Neuroscience Letters. - 0304-3940. ; 300:3, s. 157-160
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Tidskriftsartikel (refereegranskat)abstract
- The clinical significance and the effects of pharmacological treatment of patients with Alzheimer's disease (AD) were evaluated by measurement of acetylcholinesterase (AChE) in the cerebrospinal fluid (CSF). CSF-AChE of AD patients was lower, not significantly, compared with controls. However, CSF-AChE was significantly increased after treatment of AD patients with AChE inhibitors (donepezil and galantamine). The increase was higher in patients treated with donezepil than in those treated with galantamine, which might be related to different mechanisms for the substances. The increase was also dose-dependent, and was especially marked in patients showing a clinical response. These data suggest that CSF biomarkers are capable not only of identifying a biochemical effect of drugs, but also of differentiating between different compounds in a dose-dependent manner.
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| 7. |
- Hesse, C, et al.
(författare)
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Measurement of apolipoprotein E (apoE) in cerebrospinal fluid
- 2000
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Ingår i: Neurochemical Research. - 1573-6903. ; 25:4, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E (apoE) is a protein involved in transport of lipids and has been implicated to play an important role in regeneration after nerve injury. Determination of apoE in cerebrospinal fluid (CSF) thus have a potential interest when studying different forms of brain damage and as a marker of ongoing regenerative processes in the brain. However, previous studies on CSF-ApoE in Alzheimer's disease (AD) have given inconclusive results. Such inconsistent results might be related to confounding factors interfering with sample handling and/or analyses, which have not been fully elucidated. We therefore examined different potential confounding factors for analyses of apoE in CSF and also developed a new enzyme linked immunosorbent assay (ELISA). The hydrophobic character of ApoE resulted in adsorption to different types of test tubes commonly used for collection of CSF at lumbar puncture, resulting in falsely low levels. This makes CSF handling critical, especially if samples are taken in different types of tubes, or is transferred to new tubes. Taking this confounding factors in consideration and analysing patient and control CSF handled in the same way and using the new ELISA, we could confirm our previous finding of reduced levels of ApoE in AD, (3.4 +/- 1.3 mg/l) compared with controls (4.5 +/- 2.7 mg/l) (p = 0.045). Both in the AD and in the control group, higher levels of CSF-ApoE was found in individuals possessing the ApoE4 alleles. Our results support that CSF-ApoE is reduced in AD, and that handling of CSF is a critical factor, which may explain the discrepant results from previous studies. Differences in the amount of patients and controls possessing the ApoE4 allele included might also increase the variance between different studies.
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| 8. |
- Johansson, A, et al.
(författare)
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Increased frequency of a new polymorphism in the cycle 2 (cdc2) gene in patients with Alzheimer's disease frontotemporal dementia
- 2003
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Ingår i: Neuroscience Letters. - 0304-3940. ; 340:1, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- Recent studies show linkage between Alzheimer's disease (AD) and two loci on chromosome 10. The cell division cycle 2 (cdc2) gene is located close to one of the chromosome 10 markers, and is a candidate gene for AD since it is involved in the pathogenesis of AD. We sequenced coding exons and flanking intronic sequences and the promoter region on the cdc2 gene and found three new single nucleotide polymorphisms (SNPs). We analyzed 272 Caucasian AD cases, 160 controls and 70 cases with frontotemporal dementia (FTD) for these SNPs. Homozygosity for one of the SNPs (Ex6 + 7I/D) was more frequent in both AD and FTD cases than in controls. In the combined tauopathy (AD and FTD) group the odds ratio (OR) was 1.77 (95% CI 1.19-2.63) for the Ex6 + 7II genotype. Our findings suggest that the Ex6 + 7I allele is associated with tauopathies, both AD and FrD. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.
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| 9. |
- Olsson, A, et al.
(författare)
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Measurement of alpha- and beta-secretase cleaved amyloid precursor protein in cerebrospinal fluid from Alzheimer patients
- 2003
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Ingår i: Experimental Neurology. - 0014-4886. ; 183, s. 74-
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Tidskriftsartikel (refereegranskat)abstract
- One of the major histopathological hallmarks of Alzheimer's disease (AD) is redundant senile plaques mainly composed of beta-amyloid (Abeta) aggregates. Alternative cleavage of the amyloid precursor protein (APP), occurring in both normal and AD subjects, results in the generation and secretion of soluble APP (sAPP) and Abeta. We examined the cerebrospinal fluid (CSF) for alpha- and beta-secretase cleaved sAPP (alpha-sAPP and beta-sAPP) in 81 sporadic AD patients, 19 patients with mild cognitive impairment, and 42 healthy controls by using newly developed sandwich enzyme-linked immunosorbent assay methods. We found that neither the level of CSF-alpha-sAPP nor CSF-beta-sAPP differed between sporadic AD patients and healthy controls. These findings further support the conclusion that there is no change in APP expression in sporadic AD. However, the level of CSF-beta-sAPP was significantly increased in patients with mild cognitive impairment compared to controls. We also investigated the relationship between the CSF level of alphabeta-sAPP and Abeta(42) and the apoE epsilon4 (apoFA.) allele. Significantly lower levels of CSF-alpha-sAPP were found in AD patients possessing one or two apoE4 alleles than in those not possessing the apoE4 allele. Neither the levels of CSF-beta-sAPP nor CSF-Abeta(42) differed when comparing ApoE4 allele-positive with allele-negative individuals. (C) 2003 Elsevier Science (USA). All rights reserved.
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| 10. |
- Parnetti, L, et al.
(författare)
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Cerebrospinal fluid levels of biomarkers and activity of acetylcholinesterase (AChE) and butyrylcholinesterase in AD patients before and after treatment with different AChE inhibitors
- 2002
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Ingår i: Neurological Sciences. - : Springer Science and Business Media LLC. - 1590-1874 .- 1590-3478. ; 23, s. 95-96
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Tidskriftsartikel (refereegranskat)abstract
- In order to evaluate the biochemical effects of long-term treatment with inhibitors of acetylcholinesterase (AChE) in patients with Alzheimer's disease (AD), we measured the activities of AChE and butyry1cholinesterase (BuChe) and the concentrations of beta-amyloid (1-42), tau and phosphorylated tau proteins in the cerebrospinal fluid (CSF). A total of 91 patients suffering from probable AD of mild to moderate degree were treated for 6 months with donepezil (n=59), galantamine (n=15), rivastigmine (n=10), or placebo (n=7). AChE activity in CSF was significantly increased after treatment with donepezil and galantamine; the opposite was observed in the rivastigmine-treated group. Untreated patients did not show any AChE activity variation. BuChE did not show any change in any of the groups studied. Mean values of beta-amyloid(1-42), total tau and phosphorylated tau also did not vary significantly. We conclude that AChE inhibitors induce different effects on CSF AChE activity, while other CSF biomarkers are not significantly affected by treatment.
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