1,721,031 research outputs found
Der Einsatz von Künstlicher Intelligenz bei Alzheimer-Krankheit – Personalisierte Diagnostik und Therapie
No full textAminoterminally Truncated and Oxidized Amyloid-β Peptides in the Cerebrospinal Fluid of Alzheimer's Disease Patients
No full textCarboxyterminally elongated and aminoterminally truncated amyloid-beta (A beta) peptides and their oxidized derivates are major constituents of human amyloid plaques. The objective of the present study was to clarify the diagnostic impact of the A beta peptides 1-38(ox), 2-40, and 2-42 peptides on the neurochemical cerebrospinal fluid (CSF) diagnosis of Alzheimer's disease (AD). For this purpose, 22 patients with AD and 20 non-demented disease controls (NDC) were comparatively analyzed for their cerebrospinal fluid pattern of A beta(ox)(1-38), A beta(2-40), and A beta(2-42) along with A beta(1-37), A beta(1-38), A beta(1-39), A beta(1-40), A beta(ox)(1-40), and A beta(1-42) using a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and subsequent analysis in the A beta-SDS-PAGE/immunoblot. The A beta peptides 1-38(ox), 2-40, and 2-42 could not be consistently detected in the investigated CSF samples, which applied to samples from AD and NDC patients alike. Otherwise, our approach revealed a striking decrease of A beta(1-42) and A beta(2-42), but not of A beta(ox)(1-38) and A beta(2-40) in AD. Both A beta(1-42) and A beta(2-42) reached reasonable accuracies for diagnosing AD alone as well as in relation to A beta(1-40), A beta(1-38), or the sum of all measured A beta peptides. A beta(ox)(1-38) was negatively correlated to the Mini-Mental Status Examination score of AD patients, indicating that this peptide to linked to disease severity. We conclude that an exact analysis of CSF A beta peptides regarding their carboxy-and aminoterminus as well as posttranslational modification may be a promising approach for diagnosing and tracking AD.EU [115009, 246513]; State government of North Rhine-Westphali
The association of body mass index and body composition with plasma amyloid beta levels
No full textAbstract Blood-based analysis of amyloid-β is increasingly applied to incrementally establish diagnostic tests for Alzheimer’s disease. To this aim, it is necessary to determine factors that can alter blood-based concentrations of amyloid-β. We cross-sectionally analysed amyloid-β-40 and amyloid-β-42 concentrations and the 40/42 ratio in 440 community-dwelling adults and associations with body mass index, waist-to-height ratio and body composition assessed using bioelectrical impedance analysis. Body mass index and waist-to-height ratio were inversely associated with plasma amyloid-β-42 concentrations. Body fat mass, but not body cell mass and extracellular mass, was inversely associated with amyloid-β-42 levels. The results indicate that plasma concentrations of amyloid-β-42 are lower in those with increased body mass index and body fat, and associations with amyloid-β-40 did not reach significance after controlling for multiple testing. The findings support the use of body mass index as an easy-to-measure factor that should be accounted for in diagnostic models for plasma amyloid-β
The Use and Understanding of Mild Cognitive Impairment in Routine Specialist Care: A Survey Among German Memory Clinics
No full textObjectives: Mild cognitive impairment (MCI) is a heterogeneous clinical syndrome and is important for the diagnosis and management of Alzheimer’s disease (AD). With the expansion of biomarker-based diagnostics, the aim of this study is to clarify the current attitudes towards and the use of MCI, and MCI due to AD, in German memory clinics. Methods: An online survey (50 items) was performed in 2022 among specialized clinicians (N = 45) in German memory clinics to assess the use of MCI and biomarkers in current diagnosis and treatment. Attitudinal and frequency items were assessed with a five-point numeric scale (strongly disagree = 1 to completely agree = 5 and never = 1 to always = 5, respectively). Results: All respondents used MCI as a clinical diagnosis. The benefits of diagnosing MCI were labeling deficits as disease symptoms (M = 4.4, SD = 0.7), improving coping with symptoms (M = 4.1, SD = 0.9), and motivating risk reduction activities (M = 4.0, SD = 0.9). Overall, 37 respondents used specialized diagnostic criteria for MCI due to AD, and all had access to biomarker diagnostics. Patients with MCI due to AD received more frequent counseling on memory training (p < 0.001), other non-pharmacological treatments (p < 0.001), and antidementive drug treatment (p < 0.001) than patients with MCI of other etiologies. Acetylcholinesterase inhibitors were prescribed significantly more frequently to patients with MCI due to AD (p < 0.001) compared to other MCI patients. Conclusions: MCI is commonly used as a clinical diagnosis in German memory clinics. AD biomarker assessment is well established and influences patient counseling and treatment recommendations
Molecular Biology of Alzheimer’s Dementia and Its Clinical Relevance to Early Diagnosis and New Therapeutic Strategies
No full textOver the past few years, molecular biological research has considerably deepened our understanding of the pathophysiological basis of Alzheimer’s dementia (AD). Although different genetic origins of the disease have been identified, all of the findings point to a common terminal sequence in familial AD. This consists of an increased production of β-amyloid peptides from β-amyloid precursor protein. For the cases of sporadic AD, which far outweigh the number of cases of familial AD, an impaired catabolism of the β-amyloid peptides may also be pathophysiologically decisive according to the latest findings. Research into the molecular level of AD makes it possible to identify points of attack for rational drug treatment of the disease, while molecular markers of AD are increasingly being used as a part of early and differential neurochemical diagnostics
Correction to: Cerebrospinal fluid amyloid-β 2-42 is decreased in Alzheimer’s, but not in frontotemporal dementia
No full textCerebrospinal fluid amyloidβ peptide patterns in Alzheimer's disease patients and nondemented controls depend on sample pretreatment: Indication of carrier-mediated epitope masking of amyloidβ peptides
No full textA quantitative urea-based amyloid β (Aβ)-sodium dodecyl sulfate-polyacrylamide gel electrophoresis with Western immunoblot (Aβ-SDS-PAGE/immunoblot) reveals highly conserved and disease-specific Aβ peptide patterns (Aβ 1-37, 1-38, 1-39, 1-40, 1-42) in Alzheimer's disease (AD) patients and nondemented controls. For further standardization of this method, we analyzed cerebrospinal fluid (CSF) of eight probable AD patients and seven nondemented controls using different preanalytical procedures for Aβ-SDS-PAGE/immunoblot and Aβ1-42-enzyme linked immunosorbent assay (ELISA). Both diagnostic groups were discriminated significantly by absolute levels of Aβ1-42 and ratios of Aβ1-42/40, 1-42/38, 1-42/39. Preanalytical freezing of CSF led to a highly significant loss of all Aβ peptide species. This effect was most pronounced for Aβ1-42 and completely prevented by SDS-heat denaturation prior to freezing. Prolonged storage of SDS-heat denatured CSF led to a selective loss of Aβ1-42 and impaired the discrimination of diagnostic groups as measured by Aβ-SDS-PAGE/immunoblot. Neither freezing nor storage significantly affected absolute Aβ1-42 levels as determined by Aβ1-42-ELISA, but both impaired the discrimation of diagnostic groups. Hence, we suggest immediate analysis of samples for Aβ1-42-ELISA, analysis after a short freezing interval for Aβ-SDS-PAGE/immunoblot, and avoidance of prolonged storage intervals. Remarkably, Aβ-SDS-PAGE/immunoblot measured threefold higher levels of Aβ1-42 in CSF than Aβ1-42-ELISA. In summary, our results indicate carrier-mediated epitope masking of Aβ1-42
Plasma Amyloid-BetaPeptides in Acute Cerebral Ischemia: A Pilot Study
No full textBackground Blood-based tests for a rapid and valid diagnosis as well as outcome prognosis of acute stroke are desirable. Recently, plasma A beta 40 was suggested as an independent cerebrovascular risk factor candidate. Methods We investigated eight plasma samples of patients with clinical signs of acute cerebral ischemia for derangements of plasma amyloid-beta (A beta) peptide patterns as compared to 13 patients with other neuropsychiatric diseases. For the analysis of plasma, we used immunoprecipitation followed by the quantitative A beta-SDS-PAGE/immunoblot. Results The major outcome was a striking decrease of A beta 140 in plasma paralleled by an increase in the ratio of A beta 138/A beta 140 in two patients with acute stroke. Interestingly, these patients had an onset of symptoms within only 24 hr before venous puncture and there was a strong correlation of A beta 138/A beta 140 levels with the time span between onset of symptoms and venous puncture. Conclusion From these results, we suggest the ratio of plasma A beta 138/A beta 140 as a possible biomarker for the early diagnosis of acute stroke. J. Clin. Lab. Anal. 26:238-245, 2012. (c) 2012 Wiley Periodicals, Inc
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