| 1. |
- Andreasen, Niels, et al.
(författare)
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Amyloid-related biomarkers for Alzheimer's disease.
- 2008
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Ingår i: Current medicinal chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673. ; 15:8, s. 766-71
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Forskningsöversikt (refereegranskat)abstract
- Alzheimer's disease (AD) is an age-related disorder that causes brain damage resulting in progressive cognitive impairment and death. Three decades of progress have given us a detailed understanding of the underlying molecular mechanisms. Over the past 10 years, this knowledge has translated into a range of targets for therapy, the most promising of which is amyloid beta (Abeta). An imbalance between the production and clearance of Abeta is thought by many to represent the earliest event in the pathogenesis of AD. Abeta is known to be subject to oligomerisation, a process that increases its synaptotoxicity. The oligomers may aggregate further to proto-fibrils and fibrils, eventually forming senile plaques, the neuropathological hallmark of AD. In this article we review the key aspects of Abeta as a biomarker for AD, including its pathogenicity, the diagnostic performance of different Abeta assays in different settings, and the potential usefulness of Abeta as a surrogate marker for treatment efficacy in clinical trials of novel Abeta-targeting drugs.
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| 2. |
- Andreasson, Ulf, 1968, et al.
(författare)
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Analytical aspects of molecular Alzheimer's disease biomarkers
- 2012
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Ingår i: Biomarkers in Medicine. - : Future Medicine Ltd. - 1752-0363 .- 1752-0371. ; 6:4, s. 377-389
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Forskningsöversikt (refereegranskat)abstract
- In general, a biomarker has multiple uses such as a diagnostic tool and a method to monitor therapy. The quality of a biomarker depends on how big the difference is between, for example, patients and healthy controls, but also on the capacity of the method used to measure it (the uncertainty in the method should be much less than the difference between the groups). A good biomarker should also be specific towards a disease, allowing for differentiation between clinically related syndromes. In addition, it is of importance that the stability of the methods used is high enough to establish cut-off levels both in individual laboratories and on a global scale. In the field of Alzheimer's disease, there are currently three cerebrospinal fluid markers that have been verified in multiple studies and the analytical aspects of measuring them will be discussed.
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| 3. |
- Andreasson, Ulf, 1968, et al.
(författare)
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Aspects of beta-amyloid as a biomarker for Alzheimer's disease
- 2007
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Ingår i: Biomarkers in Medicine. - : Future Medicine Ltd. - 1752-0363 .- 1752-0371. ; 1:1, s. 59-78
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Forskningsöversikt (refereegranskat)abstract
- Alzheimer’s disease is an age-related neurodegenerative disorder that results in progressive cognitive impairment and death. The accumulation of β-amyloid (Aβ) in specific brain regions is believed by many to represent the earliest event in the pathogenesis of the disease. Here, we review the key aspects of Aβ as a biomarker for Alzheimer’s disease, including the pathogenicity of Aβ, the possible biological functions of its precursor protein, the Aβ metabolism and homeostasis, the diagnostic performance of different Aβ assays in different settings and the potential usefulness of Aβ as a surrogate marker for treatment efficacy in clinical trials of novel Aβ-targeting drugs against Alzheimer’s disease.
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| 4. |
- Ashton, Nicholas J., et al.
(författare)
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An update on blood-based biomarkers for non-Alzheimer neurodegenerative disorders.
- 2020
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Ingår i: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 16
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Forskningsöversikt (refereegranskat)abstract
- Cerebrospinal fluid analyses and neuroimaging can identify the underlying pathophysiology at the earliest stage of some neurodegenerative disorders, but do not have the scalability needed for population screening. Therefore, a blood-based marker for such pathophysiology would have greater utility in a primary care setting and in eligibility screening for clinical trials. Rapid advances in ultra-sensitive assays have enabled the levels of pathological proteins to be measured in blood samples, but research has been predominantly focused on Alzheimer disease (AD). Nonetheless, proteins that were identified as potential blood-based biomarkers for AD, for example, amyloid-β, tau, phosphorylated tau and neurofilament light chain, are likely to be relevant to other neurodegenerative disorders that involve similar pathological processes and could also be useful for the differential diagnosis of clinical symptoms. This Review outlines the neuropathological, clinical, molecular imaging and cerebrospinal fluid features of the most common neurodegenerative disorders outside the AD continuum and gives an overview of the current status of blood-based biomarkers for these disorders.
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| 5. |
- Ashton, Nicholas J., et al.
(författare)
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Salivary Biomarkers for Alzheimer's Disease and Related Disorders.
- 2019
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Ingår i: Neurology and therapy. - : Springer Science and Business Media LLC. - 2193-8253 .- 2193-6536. ; 8:Suppl 2, s. 83-94
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Forskningsöversikt (refereegranskat)abstract
- The search for accessible and cost-effective biomarkers to complement current cerebrospinal fluid (CSF) and imaging biomarkers in the accurate detection of Alzheimer disease (AD) and other common neurodegenerative disorders remains a challenging task. The advances in ultra-sensitive detection methods has highlighted blood biomarkers (e.g. amyloid-β and neurofilament light) as a valuable and realistic tool in a diagnostic or screening process. Saliva, however, is also a rich source of potential biomarkers for disease detection and offers several practical advantages over biofluids that are currently examined for neurodegenerative disorders. However, while this may be true for the general population, challenges in collecting saliva from an elderly population should be seriously considered. In this review, we begin by discussing how saliva is produced and how age-related conditions can modify saliva production and composition. We then focus on the data available which support the concept of salivary amyloid-β, tau species and novel biomarkers in detecting AD and alpha-synuclein (α-syn) in Parkinson's disease (PD).
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| 6. |
- Blennow, Kaj, 1958, et al.
(författare)
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Alzheimer's disease.
- 2006
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Ingår i: Lancet. - 1474-547X. ; 368:9533, s. 387-403
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Forskningsöversikt (refereegranskat)abstract
- Alzheimer's disease is the most common cause of dementia. Research advances have enabled detailed understanding of the molecular pathogenesis of the hallmarks of the disease--ie, plaques, composed of amyloid beta (Abeta), and tangles, composed of hyperphosphorylated tau. However, as our knowledge increases so does our appreciation for the pathogenic complexity of the disorder. Familial Alzheimer's disease is a very rare autosomal dominant disease with early onset, caused by mutations in the amyloid precursor protein and presenilin genes, both linked to Abeta metabolism. By contrast with familial disease, sporadic Alzheimer's disease is very common with more than 15 million people affected worldwide. The cause of the sporadic form of the disease is unknown, probably because the disease is heterogeneous, caused by ageing in concert with a complex interaction of both genetic and environmental risk factors. This seminar reviews the key aspects of the disease, including epidemiology, genetics, pathogenesis, diagnosis, and treatment, as well as recent developments and controversies.
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| 7. |
- Blennow, Kaj, 1958, et al.
(författare)
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Cerebrospinal fluid and plasma biomarkers in Alzheimer disease
- 2010
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Ingår i: Nature reviews. Neurology. - : Springer Science and Business Media LLC. - 1759-4766 .- 1759-4758. ; 6:3, s. 131-44
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Forskningsöversikt (refereegranskat)abstract
- Intense multidisciplinary research has provided detailed knowledge of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new therapeutic strategies with putative disease-modifying effects. Several of the most promising approaches, such as amyloid-beta immunotherapy and secretase inhibition, are now being tested in clinical trials. Disease-modifying treatments might be at their most effective when initiated very early in the course of AD, before amyloid plaques and neurodegeneration become too widespread. Thus, biomarkers are needed that can detect AD in the predementia phase or, ideally, in presymptomatic individuals. In this Review, we present the rationales behind and the diagnostic performances of the core cerebrospinal fluid (CSF) biomarkers for AD, namely total tau, phosphorylated tau and the 42 amino acid form of amyloid-beta. These biomarkers reflect AD pathology, and are candidate markers for predicting future cognitive decline in healthy individuals and the progression to dementia in patients who are cognitively impaired. We also discuss emerging plasma and CSF biomarkers, and explore new proteomics-based strategies for identifying additional CSF markers. Furthermore, we outline the roles of CSF biomarkers in drug discovery and clinical trials, and provide perspectives on AD biomarker discovery and the validation of such markers for use in the clinic.
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| 8. |
- Blennow, Kaj, 1958, et al.
(författare)
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Cerebrospinal Fluid Biomarkers for Alzheimer's Disease.
- 2009
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Ingår i: Journal of Alzheimer's disease : JAD. - 1387-2877. ; 18:2, s. 413-17
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Forskningsöversikt (refereegranskat)abstract
- Research progress has given detailed knowledge on the molecular pathogenesis of Alzheimer's disease (AD), which has been translated into an ongoing development of disease-modifying treatments. These new drug candidates are targeted on inhibiting amyloid-beta (Abeta) production and aggregation or tau aggregation. If these drugs prove to be efficient, diagnostic tools enabling early diagnosis of AD will be of great value. Also in drug development, it is important to co-develop biomarkers to serve as tools to identify and monitor the biochemical effect of the drug directly in patients. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). The core candidate CSF biomarkers Abeta_{42}, total tau (T-tau), and phosphorylated tau (P-tau) have been shown to have a high diagnostic performance to identify AD also in the early phase of the disease. This paper reviews recent research advances on these CSF biomarkers for use in clinical diagnosis and in clinical trials in AD.
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| 9. |
- Blennow, Kaj, 1958, et al.
(författare)
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Is it time for biomarker-based diagnostic criteria for prodromal Alzheimer's disease?
- 2010
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 2:2
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Forskningsöversikt (refereegranskat)abstract
- ABSTRACT: Drug candidates targeting amyloid-beta (Abeta) pathology in Alzheimer's disease are in different phases of clinical trials. These treatments will probably be most effective in the earlier stages of the disease, before neurodegeneration is too severe, but at the same time symptoms are vague and the clinical diagnosis is difficult. Recent research advances have resulted in promising biomarkers, including cerebrospinal fluid analyses for tau and Abeta, magnetic resonance imaging measurement of atrophy, and positron emission tomography imaging of glucose metabolism and Abeta pathology, which allow identification of prodromal Alzheimer's disease. More details are needed, however, on how these biomarkers can be standardized, to allow a general implementation in the clinical routine diagnostic work-up of patients with cognitive disturbances.
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| 10. |
- Blennow, Kaj, 1958, et al.
(författare)
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Pinpointing plaques with PIB.
- 2006
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 12:7, s. 753-4; discussion 754
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Forskningsöversikt (refereegranskat)
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