| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Mattsson, N., et al.
(författare)
-
Clinical validity of cerebrospinal fluid A beta 42, tau, and phospho-tau as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework
- 2017
-
Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 52, s. 196-213
-
Tidskriftsartikel (refereegranskat)abstract
- Novel diagnostic criteria for Alzheimer's disease (AD) incorporate biomarkers, but their maturity for implementation in clinical practice at the prodromal stage (mild cognitive impairment [ MCI]) is unclear. Here, we evaluate cerebrospinal fluid (CSF) beta-amyloid42 (A beta 42), total tau, and phosphorylated tau in the light of a 5-phase framework for biomarker development. Ample evidence is available for phase 1 (identifying useful leads) and phase 2 (assessing the accuracy for AD dementia versus controls) for CSF biomarkers. Phase 3 (utility in MCI) is partially achieved. In cohorts with long follow-up time, CSF A beta 42, total tau, and phosphorylated tau have high diagnostic accuracy for MCI due to AD. Phase 4 (performance in real world) is ongoing, and phase 5 studies (quantify impact and costs) are to come. Our results highlight priorities to pursue and to enable the proper use of CSF biomarkers in the clinic. Priorities are to reduce measurement variability by introduction of fully automated assay systems; to increase diagnostic specificity toward non-AD neurocognitive diseases at the MCI stage; and to clarify the role of CSF biomarkers versus other biomarker modalities in clinical practice and in design of clinical trials. These efforts are currently ongoing. (C) 2016 Elsevier Inc. All rights reserved.
|
|
| 7. |
|
|
| 8. |
- Rye, Phil D., et al.
(författare)
-
A Novel Blood Test for the Early Detection of Alzheimer's Disease
- 2011
-
Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 23:1, s. 121-129
-
Tidskriftsartikel (refereegranskat)abstract
- Despite a variety of testing approaches, it is often difficult to make an accurate diagnosis of Alzheimer's disease (AD), especially at an early stage of the disease. Diagnosis is based on clinical criteria as well as exclusion of other causes of dementia but a definitive diagnosis can only be made at autopsy. We have investigated the diagnostic value of a 96-gene expression array for detection of early AD. Gene expression analysis was performed on blood RNA from a cohort of 203 probable AD and 209 cognitively healthy age matched controls. A disease classification algorithm was developed on samples from 208 individuals (AD = 103; controls = 105) and was validated in two steps using an independent initial test set (n = 74; AD= 32; controls = 42) and another second test set (n = 130; AD= 68; controls = 62). In the initial analysis, diagnostic accuracy was 71.6 +/- 10.3%, with sensitivity 71.9 +/- 15.6% and specificity 71.4 +/- 13.7%. Essentially the same level of agreement was achieved in the two independent test sets. High agreement (24/30; 80%) between algorithm prediction and subjects with available cerebrospinal fluid biomarker was found. Assuming a clinical accuracy of 80%, calculations indicate that the agreement with underlying true pathology is in the range 85%-90%. These findings suggest that the gene expression blood test can aid in the diagnosis of mild to moderate AD, but further studies are needed to confirm these findings.
|
|
| 9. |
|
|
