Biomarker-guided clustering of Alzheimer’s disease clinical syndromes
- Title
- Biomarker-guided clustering of Alzheimer’s disease clinical syndromes
- Author
- 김승현
- Keywords
- Alzheimer's disease; Biomarker-guided categorization; Clustering; Pathophysiology; Precision medicine
- Issue Date
- 2020-01
- Publisher
- ELSEVIER SCIENCE INC
- Citation
- NEUROBIOLOGY OF AGING, v. 83, page. 42-53
- Abstract
- Alzheimer's disease (AD) neuropathology is extremely heterogeneous, and the evolution from preclinical to mild cognitive impairment until dementia is driven by interacting genetic/biological mechanisms not fully captured by current clinical/research criteria. We characterized the heterogeneous "construct" of AD through a cerebrospinal fluid biomarker-guided stratification approach. We analyzed 5 validated pathophysiological cerebrospinal fluid biomarkers (A beta(1-42), t-tau, -p-tau(181), NFL, YKL-40) in 113 participants (healthy controls [N = 20], subjective memory complainers [N = 36], mild cognitive impairment [N = 20], and AD dementia [N = 37], age: 66.7 +/- 10.4, 70.4 +/- 7.7, 71.7 +/- 8.4, 76.2 +/- 3.5 years [mean +/- SD], respectively) using Density-Based Spatial Clustering of Applications with Noise, which does not require a priori determination of the number of clusters. We found 5 distinct clusters (sizes: N = 38, 16, 24, 14, and 21) whose composition was independent of phenotypical groups. Two clusters showed biomarker profiles linked to neurodegenerative processes not associated with classical AD-related pathophysiology. One cluster was characterized by the neuroinflammation biomarker YKL-40. Combining nonlinear data aggregation with informative biomarkers can generate novel patient strata which are representative of cellular/molecular pathophysiology and may aid in predicting disease evolution and mechanistic drug response. (C) 2019 The Authors. Published by Elsevier Inc.
- URI
- https://www.sciencedirect.com/science/article/pii/S0197458019303185?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/160942
- ISSN
- 0197-4580; 1558-1497
- DOI
- 10.1016/j.neurobiolaging.2019.08.032
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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