Ting-Bin Chen1,2,3,4, Yu-Hua Lai5, Ting-Ling Ke1, Jun-Peng Chen6, Yi-Jung Lee1,7, Szu-Ying Lin8, Po-Chen Lin9, Pei-Ning Wang9,10,11, Irene H Cheng12,13. 1. Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan. 2. Department of Neurology, Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan. 3. Dementia and Parkinson's Disease Integrated Center, Taichung Veterans General Hospital, Taichung, Taiwan. 4. Center for Geriatrics and Gerontology, Taichung Veterans General Hospital, Taichung, Taiwan. 5. Department of Neurology, Cheng-Hsin General Hospital, Taipei, Taiwan. 6. Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan. 7. Division of Neurology, Department of Medicine, Taipei City Hospital Renai Branch, Taipei, Taiwan. 8. Taipei Municipal Gan-Dau Hospital, Taipei, Taiwan. 9. Division of General Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan. 10. Aging and Health Research Center, National Yang-Ming University, Taipei, Taiwan. 11. Brain Research Center, National Yang-Ming University, Taipei, Taiwan. 12. Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan, ihjcheng@gmail.com. 13. Brain Research Center, National Yang-Ming University, Taipei, Taiwan, ihjcheng@gmail.com.
Abstract
BACKGROUND: Changes in cerebrospinal fluid, neuroimaging, and cognitive functions have been used as diagnostic biomarkers of Alzheimer's disease (AD). This study aimed to investigate the temporal trajectories of plasma biomarkers in subjects with mild cognitive impairment (MCI) and patients with AD relative to healthy controls (HCs). METHODS: In this longitudinal study, 82 participants (31 HCs, 33 MCI patients, and 18 AD patients) were enrolled. After 3 years, 7 HCs had transitioned to MCI and 10 subjects with MCI had converted to AD. We analyzed plasma amyloid beta (Aβ) and tau proteins at baseline and annually to correlate with biochemical data and neuropsychological scores. RESULTS: Longitudinal data analysis showed an evolution of Aβ-related biomarkers over time within patients, whereas tau-related biomarkers differed primarily across diagnostic classifications. An initial steady increase in Aβ42 in the MCI stage was followed by a decrease just prior to clinical AD onset. Hyperphosphorylated tau protein levels correlated with cognitive decline in the MCI stage, but not in the AD stage. CONCLUSION: Plasma Aβ and tau levels change in a dynamic, nonlinear, nonparallel manner over the AD continuum. Changes in plasma Aβ concentration are time-dependent, whereas changes in hyperphosphorylated tau protein levels paralleled the clinical progression of MCI. It remains to be clarified whether diagnostic efficiency can be improved by combining multiple plasma markers or combining plasma markers with other diagnostic biomarkers.
BACKGROUND: Changes in cerebrospinal fluid, neuroimaging, and cognitive functions have been used as diagnostic biomarkers of Alzheimer's disease (AD). This study aimed to investigate the temporal trajectories of plasma biomarkers in subjects with mild cognitive impairment (MCI) and patients with AD relative to healthy controls (HCs). METHODS: In this longitudinal study, 82 participants (31 HCs, 33 MCI patients, and 18 ADpatients) were enrolled. After 3 years, 7 HCs had transitioned to MCI and 10 subjects with MCI had converted to AD. We analyzed plasma amyloid beta (Aβ) and tau proteins at baseline and annually to correlate with biochemical data and neuropsychological scores. RESULTS: Longitudinal data analysis showed an evolution of Aβ-related biomarkers over time within patients, whereas tau-related biomarkers differed primarily across diagnostic classifications. An initial steady increase in Aβ42 in the MCI stage was followed by a decrease just prior to clinical AD onset. Hyperphosphorylated tau protein levels correlated with cognitive decline in the MCI stage, but not in the AD stage. CONCLUSION: Plasma Aβ and tau levels change in a dynamic, nonlinear, nonparallel manner over the AD continuum. Changes in plasma Aβ concentration are time-dependent, whereas changes in hyperphosphorylated tau protein levels paralleled the clinical progression of MCI. It remains to be clarified whether diagnostic efficiency can be improved by combining multiple plasma markers or combining plasma markers with other diagnostic biomarkers.
Authors: Robert D Daniels; Sean A P Clouston; Charles B Hall; Kristi R Anderson; David A Bennett; Evelyn J Bromet; Geoffrey M Calvert; Tania Carreón; Steven T DeKosky; Erica D Diminich; Caleb E Finch; Sam Gandy; William C Kreisl; Minos Kritikos; Travis L Kubale; Michelle M Mielke; Elaine R Peskind; Murray A Raskind; Marcus Richards; Mary Sano; Albeliz Santiago-Colón; Richard P Sloan; Avron Spiro; Neil Vasdev; Benjamin J Luft; Dori B Reissman Journal: Int J Environ Res Public Health Date: 2021-01-14 Impact factor: 3.390
Authors: Jordan D Marks; Jeremy A Syrjanen; Jonathan Graff-Radford; Ronald C Petersen; Mary M Machulda; Michelle R Campbell; Alicia Algeciras-Schimnich; Val Lowe; David S Knopman; Clifford R Jack; Prashanthi Vemuri; Michelle M Mielke Journal: Alzheimers Res Ther Date: 2021-12-14 Impact factor: 6.982