| Autor: |
Samantha Prins, Ahnjili Zhuparris, Ellen P. Hart, Robert-Jan Doll, Geert Jan Groeneveld |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Alzheimer’s Research & Therapy, Vol 13, Iss 1, Pp 1-11 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
1758-9193 |
| DOI: |
10.1186/s13195-021-00874-9 |
| Popis: |
Abstract Background In the current study, we aimed to develop an algorithm based on biomarkers obtained through non- or minimally invasive procedures to identify healthy elderly subjects who have an increased risk of abnormal cerebrospinal fluid (CSF) amyloid beta42 (Aβ) levels consistent with the presence of Alzheimer’s disease (AD) pathology. The use of the algorithm may help to identify subjects with preclinical AD who are eligible for potential participation in trials with disease modifying compounds being developed for AD. Due to this pre-selection, fewer lumbar punctures will be needed, decreasing overall burden for study subjects and costs. Methods Healthy elderly subjects (n = 200; age 65–70 (N = 100) and age > 70 (N = 100)) with an MMSE > 24 were recruited. An automated central nervous system test battery was used for cognitive profiling. CSF Aβ1-42 concentrations, plasma Aβ1-40, Aβ1-42, neurofilament light, and total Tau concentrations were measured. Aβ1-42/1-40 ratio was calculated for plasma. The neuroinflammation biomarker YKL-40 and APOE ε4 status were determined in plasma. Different mathematical models were evaluated on their sensitivity, specificity, and positive predictive value. A logistic regression algorithm described the data best. Data were analyzed using a 5-fold cross validation logistic regression classifier. Results Two hundred healthy elderly subjects were enrolled in this study. Data of 154 subjects were used for the per protocol analysis. The average age of the 154 subjects was 72.1 (65–86) years. Twenty-four (27.3%) were Aβ positive for AD (age 65–83). The results of the logistic regression classifier showed that predictive features for Aβ positivity/negativity in CSF consist of sex, 7 CNS tests, and 1 plasma-based assay. The model achieved a sensitivity of 70.82% (± 4.35) and a specificity of 89.25% (± 4.35) with respect to identifying abnormal CSF in healthy elderly subjects. The receiver operating characteristic curve showed an AUC of 65% (± 0.10). Conclusion This algorithm would allow for a 70% reduction of lumbar punctures needed to identify subjects with abnormal CSF Aβ levels consistent with AD. The use of this algorithm can be expected to lower overall subject burden and costs of identifying subjects with preclinical AD and therefore of total study costs. Trial registration ISRCTN.org identifier: ISRCTN79036545 (retrospectively registered). |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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