| 1. |
- Ashton, Nicholas J., et al.
(författare)
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Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer's trial selection and disease monitoring.
- 2022
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Ingår i: Nature medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 28:12, s. 2555-2562
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Tidskriftsartikel (refereegranskat)abstract
- Blood biomarkers indicative of Alzheimer's disease (AD) pathology are altered in both preclinical and symptomatic stages of the disease. Distinctive biomarkers may be optimal for the identification of AD pathology or monitoring of disease progression. Blood biomarkers that correlate with changes in cognition and atrophy during the course of the disease could be used in clinical trials to identify successful interventions and thereby accelerate the development of efficient therapies. When disease-modifying treatments become approved for use, efficient blood-based biomarkers might also inform on treatment implementation and management in clinical practice. In the BioFINDER-1 cohort, plasma phosphorylated (p)-tau231 and amyloid-β42/40 ratio were more changed at lower thresholds of amyloid pathology. Longitudinally, however, only p-tau217 demonstrated marked amyloid-dependent changes over 4-6years in both preclinical and symptomatic stages of the disease, with no such changes observed in p-tau231, p-tau181, amyloid-β42/40, glial acidic fibrillary protein or neurofilament light. Only longitudinal increases of p-tau217 were also associated with clinical deterioration and brain atrophy in preclinical AD. The selective longitudinal increase of p-tau217 and its associations with cognitive decline and atrophy was confirmed in an independent cohort (Wisconsin Registry for Alzheimer's Prevention). These findings support the differential association of plasma biomarkers with disease development and strongly highlight p-tau217 as a surrogate marker of disease progression in preclinical and prodromal AD, with impact for the development of new disease-modifying treatments.
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| 2. |
- Hansson, Oskar, et al.
(författare)
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Evaluation of Plasma A beta as Predictor of Alzheimer's Disease in Older Individuals Without Dementia: A Population-Based Study
- 2012
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 28:1, s. 231-238
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-beta (A beta) pathology is a major component in the mechanisms behind Alzheimer's disease (AD). Measurement of A beta(42) in cerebrospinal fluid predicts cognitive decline in patients with mild cognitive impairment and identifies AD in patients with dementia. However, studies on A beta in plasma are contradictory. In this prospective population-based study, plasma A beta(42) and A beta(40) were measured at baseline in 730 adults aged 70 years or older and without dementia. After five years, plasma levels were analyzed again and participants were assessed for development of dementia. During follow-up, 53 individuals (7%) developed dementia of which 37 (5%) were classified as AD. No difference in baseline plasma A beta(42), A beta(40), or A beta(42)/A beta(40) ratio levels were observed between converters to dementia or AD compared to the cognitively stable individuals. However, individuals with plasma A beta(40) levels above the median level for the group at baseline had an increased risk of developing dementia and AD during the follow-up, even after adjustment for age, gender, APOE genotype, and educational level (odds ratio = 2.2, 95% confidence interval = 1.0-4.7, p < 0.05). Neither plasma A beta(42) nor the A beta(42)/A beta(40) ratio influenced the risk of developing dementia or AD. Moreover, A beta(42) and A beta(40) levels increased over the 5 years, whereas the A beta(42)/A beta(40) ratio decreased (p < 0.001). In conclusion, this study suggests that measurement of plasma A beta should not be used clinically to predict dementia or AD. However, plasma A beta(40) may possibly be regarded as a moderate risk marker comparable to other risk markers for AD such as first-degree family history of dementia.
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| 3. |
- Leuzy, Antoine, et al.
(författare)
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Comparing the Clinical Utility and Diagnostic Performance of Cerebrospinal Fluid P-Tau181, P-Tau217 and P-Tau231 Assays
- 2021
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Ingår i: Neurology. - 1526-632X. ; 97:17, s. 1681-1694
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Phosphorylated tau (P-tau) in cerebrospinal fluid (CSF) is considered an important biomarker in Alzheimer's disease (AD) and has been incorporated in recent diagnostic criteria. Several variants exist, including P-tau at threonines 181 (P-tau181), 217 (P-tau217) and 231 (P-tau231). However, no studies have compared their diagnostic performance or association to amyloid-β (Aβ) and Tau positron emission tomography (PET). Understanding which P-tau variant to use remains an important yet answered question. We aimed to compare the diagnostic accuracy of P-tau181, P-tau217 and P-tau231 in CSF for AD and their association with Aβ and Tau-PET.METHODS: 629 subjects from the Swedish BioFINDER-2 study were included (cognitively unimpaired, n=334; Aβ-positive mild cognitive impairment, n=84; AD dementia, n=119; and non-AD disorders, n=92). In addition to P-tau181 and P-tau217 measured using assays with the same detector antibodies from Eli Lilly (P-tau181Lilly, P-tau217Lilly) and P-tau231, we also included P-tau181 measurements from two commonly used assays (Innotest and Elecsys).RESULTS: Though all P-tau variants increased across the AD continuum, P-tau217Lilly showed the greatest dynamic range (13-fold-increase vs 1.9-5.4-fold-increase for other P-tau variants for AD dementia vs non-AD). P-tau217Lilly showed stronger correlations with Aβ- and Tau-PET (P<0.0001). P-tau217Lilly exhibited higher accuracy than other P-tau variants for separating AD dementia from non-AD (AUC, 0.991vs 0.906-0.982, P<0.0001) and for identifying Aβ- (AUC, 0.951 vs 0.816-0.924, P<0.0001) and Tau-PET positivity (AUC, 0.957 vs 0.836-0.938, P<0.0001). Finally, P-tau181Lilly generally performed better than the other P-tau181 assays, (e.g., AD dementia vs non-AD, AUC, 0.976 vs 0.923, P<0.0001).DISCUSSION: CSF P-tau217Lilly seem to be more useful than other included P-tau assays in the work-up of AD. Varied results across P-tau181 assays also highlights the importance of anti-tau antibodies for biomarker performance.CLASSIFICATION OF EVIDENCE: This study provides class II evidence that phosphorylated tau at threonine 217 provides higher diagnostic accuracy for diagnosis of AD dementia than P-tau at threonine 181 or 231.
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