| 1. |
- Vergallo, A., et al.
(författare)
-
Association of plasma YKL-40 with brain amyloid-β levels, memory performance, and sex in subjective memory complainers
- 2020
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 96, s. 22-32
-
Tidskriftsartikel (refereegranskat)abstract
- Neuroinflammation, a key early pathomechanistic alteration of Alzheimer's disease, may represent either a detrimental or a compensatory mechanism or both (according to the disease stage). YKL-40, a glycoprotein highly expressed in differentiated glial cells, is a candidate biomarker for in vivo tracking neuroinflammation in humans. We performed a longitudinal study in a monocentric cohort of cognitively healthy individuals at risk for Alzheimer's disease exploring whether age, sex, and the apolipoprotein E ε4 allele affect plasma YKL-40 concentrations. We investigated whether YKL-40 is associated with brain amyloid-β (Aβ) deposition, neuronal activity, and neurodegeneration as assessed via neuroimaging biomarkers. Finally, we investigated whether YKL-40 may predict cognitive performance. We found an age-associated increase of YKL-40 and observed that men display higher concentrations than women, indicating a potential sexual dimorphism. Moreover, YKL-40 was positively associated with memory performance and negatively associated with brain Aβ deposition (but not with metabolic signal). Consistent with translational studies, our results suggest a potentially protective effect of glia on incipient brain Aβ accumulation and neuronal homeostasis. © 2020 Elsevier Inc.
|
|
| 2. |
- Vergallo, A., et al.
(författare)
-
Plasma amyloid beta 40/42 ratio predicts cerebral amyloidosis in cognitively normal individuals at risk for Alzheimer's disease
- 2019
-
Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:6, s. 764-775
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Blood-based biomarkers of pathophysiological brain amyloid beta (A beta) accumulation, particularly for preclinical target and large-scale interventions, are warranted to effectively enrich Alzheimer's disease clinical trials and management. Methods: We investigated whether plasma concentrations of the A beta(1-40)/A beta(1-42) ratio, assessed using the single-molecule array (Simoa) immunoassay, may predict brain A beta positron emission tomography status in a large-scale longitudinal monocentric cohort (N = 276) of older individuals with subjective memory complaints. We performed a hypothesis-driven investigation followed by a no-apriori hypothesis study using machine learning. Results: The receiver operating characteristic curve and machine learning showed a balanced accuracy of 76.5% and 81%, respectively, for the plasma A beta(1-40)/A beta(1-42) ratio. The accuracy is not affected by the apolipoprotein E (APOE) epsilon 4 allele, sex, or age. Discussion: Our results encourage an independent validation cohort study to confirm the indication that the plasma A beta(1-40)/A beta(1-42) ratio, assessed via Simoa, may improve future standard of care and clinical trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
|
|
| 3. |
|
|
| 4. |
- Hampel, H., et al.
(författare)
-
The use of lumbar puncture and safety recommendations in Alzheimer's disease: a plain language summary
- 2022
-
Ingår i: Neurodegenerative Disease Management. - : Future Medicine Ltd. - 1758-2024 .- 1758-2032. ; 12:5
-
Tidskriftsartikel (refereegranskat)abstract
- What is this summary about? This is a plain language summary of an article published in Alzheimer's & Dementia. It looks at a type of test called a lumbar puncture (also known as spinal tap) used in people suspected of having Alzheimer's disease or some other form of dementia. This summary focuses on how to do a lumbar puncture safely. Why is this important? Alzheimer's disease is a progressive condition, which means it gets worse over time. This leads to difficulties with thinking and memory. People with Alzheimer's disease show a build up of proteins called amyloid-beta and tau in the brain. This is followed by a gradual loss of brain cells and brain function. The changes in the brain are thought to occur years before symptoms appear. Lumbar puncture is a medical procedure during which samples of cerebrospinal fluid are collected. In Alzheimer's disease, it is used to examine cerebrospinal fluid biomarkers that can help diagnose disease. Lumbar puncture is traditionally considered as a painful and invasive procedure with frequent side effects. However, multiple studies indicate that a lumbar puncture can be performed safely. Side effects are typically mild and do not require specialist intervention. What are the key takeaways? Despite the low risk of serious complications associated with a lumbar puncture, physicians and their patients may be reluctant to recommend or undergo this procedure. Patient education, specialist training, as well as new methods concerning patient safety are important factors to support the widespread use of lumbar puncture in Alzheimer's disease.
|
|
| 5. |
- Hampel, H., et al.
(författare)
-
State-of-the-art of lumbar puncture and its place in the journey of patients with Alzheimer's disease
- 2022
-
Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 159-177
-
Tidskriftsartikel (refereegranskat)abstract
- Recent advances in developing disease-modifying therapies (DMT) for Alzheimer's disease (AD), and the recognition that AD pathophysiology emerges decades before clinical symptoms, necessitate a paradigm shift of health-care systems toward biomarker-guided early detection, diagnosis, and therapeutic decision-making. Appropriate incorporation of cerebrospinal fluid biomarker analysis in clinical practice is an essential step toward system readiness for accommodating the demand of AD diagnosis and proper use of DMTs-once they become available. However, the use of lumbar puncture (LP) in individuals with suspected neurodegenerative diseases such as AD is inconsistent, and the perception of its utility and safety differs considerably among medical specialties as well as among regions and countries. This review describes the state-of-the-art evidence concerning the safety profile of LP in older adults, discusses the risk factors for LP-associated adverse events, and provides recommendations and an outlook for optimized use and global implementation of LP in individuals with suspected AD.
|
|
| 6. |
- Hampel, H., et al.
(författare)
-
beta-Secretase1 biological markers for Alzheimer's disease: state-of-art of validation and qualification
- 2020
-
Ingår i: Alzheimers Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- beta -Secretase1 (BACE1) protein concentrations and rates of enzyme activity, analyzed in human bodily fluids, are promising candidate biological markers for guidance in clinical trials investigating BACE1 inhibitors to halt or delay the dysregulation of the amyloid-beta pathway in Alzheimer's disease (AD). A robust body of evidence demonstrates an association between cerebrospinal fluid/blood BACE1 biomarkers and core pathophysiological mechanisms of AD, such as brain protein misfolding and aggregration, neurodegeneration, and synaptic dysfunction.In pharmacological trials, BACE1 candidate biomarkers may be applied to a wide set of contexts of use (CoU), including proof of mechanism, dose-finding, response and toxicity dose estimation. For clinical CoU, BACE1 biomarkers show good performance for prognosis and disease prediction.The roadmap toward validation and qualification of BACE1 biomarkers requires standardized pre-analytical and analytical protocols to reduce inter-site variance that may have contributed to inconsistent results.BACE1 biomarker-drug co-development programs, including biomarker-guided outcomes and endpoints, may support the identification of sub-populations with a higher probability to benefit from BACE1 inhibitors with a reduced risk of adverse effects, in line with the evolving precision medicine paradigm.
|
|
| 7. |
- Hampel, H., et al.
(författare)
-
The AT(N) system for describing biological changes in Alzheimer's disease: a plain language summary
- 2022
-
Ingår i: Neurodegenerative Disease Management. - : Future Medicine Ltd. - 1758-2024 .- 1758-2032. ; 12:5, s. 231-239
-
Tidskriftsartikel (refereegranskat)abstract
- What is this summary about?: This is a plain language summary of an article published in Nature Reviews Neurology. It explains how Alzheimer's disease is diagnosed. It also looks at whether a newer way to assess people with Alzheimer's disease could help improve how the condition is diagnosed, monitored, and treated. Why is this important?: Alzheimer's disease is a long-term progressive brain disease that leads to difficulties with thinking and memory. It is a progressive condition, which means it gets worse over time. Biological changes occur in the brain of people with Alzheimer's disease. This includes a build-up of toxic protein clusters called amyloid plaques and tau tangles, gradual damage to the brain cells (neurodegeneration), and brain shrinkage due to loss of neurons. It is often due to multiple factors and doctors usually diagnose Alzheimer's disease by looking at a person's symptoms and ruling out other causes of dementia. However, research shows that people diagnosed in this way do not always have the biological changes in the brain that are related to Alzheimer's disease. This means that some people may be misdiagnosed. Additionally, there may be a delay in the appearance of Alzheimer's symptoms, by which point changes in the brain may be severe. For example, people with Alzheimer's disease show biological changes in the brain, years before symptoms appear. What are the key takeaways?: An assessment of biological changes in the brain, by measuring substances that indicate disease progress (biomarkers), may offer a fuller picture of a person's Alzheimer's disease, how advanced it is, and which treatments are likely to work best. A recently developed classification scheme known as the AT(N) system provides a way to assess and describe the biological changes in amyloid (A), tau (T), and neurodegeneration (N) that occur in people with Alzheimer's disease. The goal is to include biomarker testing in clinical practice to help physicians and practitioners diagnose, monitor, and treat people with Alzheimer's disease more effectively. The AT(N) system is being used for various purposes in clinical studies, and has the potential to assist physicians and practitioners in early detection, accurate diagnosis, staging, and treatment selection for people with Alzheimer's disease
|
|
| 8. |
- Baldacci, Filippo, et al.
(författare)
-
Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study.
- 2020
-
Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer's disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development.Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study).We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score.We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.
|
|
| 9. |
- Chiesa, Patrizia A, et al.
(författare)
-
Association of brain network dynamics with plasma biomarkers in subjective memory complainers.
- 2020
-
Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 88, s. 83-90
-
Tidskriftsartikel (refereegranskat)abstract
- Using a single integrated analysis, we examined the relationship between brain networks and molecular pathways in a cohort of elderly individuals at risk for Alzheimer's disease. In 205 subjective memory complainers (124 females, mean age: 75.7 ± 3.4), individual functional connectome was computed for a total of 3081 functional connections (set A) and 6 core plasma biomarkers of Alzheimer's disease (set B) were assessed. Partial least squares correlation analysis identified one dimension of population covariation between the 2 sets (p < 0.006), which we named bioneural mode. Five core plasma biomarkers and 190 functional connections presented bootstrap ratios greater than the critical value |1.96|. T-tau protein showed a trend toward significance (bootstrap resampling = 1.64). The salience, the language, the visuospatial, and the default mode networks were the strongest significant networks. We detected a strong association between network dynamics and core pathophysiological blood biomarkers. Innovative composite biomarkers, such as the bioneural mode, are promising to provide outcomes and better inform drug development and clinical practice for neurodegenerative diseases.
|
|
| 10. |
|
|
