Tengfei Guo1, Deniz Korman2, Suzanne L Baker3, Susan M Landau4, William J Jagust4. 1. Helen Wills Neuroscience Institute, University of California, Berkeley, California; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California. Electronic address: tengfei.guo@berkeley.edu. 2. Helen Wills Neuroscience Institute, University of California, Berkeley, California. 3. Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California. 4. Helen Wills Neuroscience Institute, University of California, Berkeley, California; Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, California.
Abstract
BACKGROUND: Amyloid-β (Aβ) likely plays a primary role in Alzheimer's disease pathogenesis, but longitudinal Aβ, tau, and neurodegeneration (A/T/N) measurements in the same individuals have rarely been examined to verify the temporal dynamics of these biomarkers. METHODS: In this study, we investigated the temporal ordering of Aβ, tau, and neurodegeneration using longitudinal biomarkers in nondemented elderly individuals. A total of 395 cognitively unimpaired individuals and 204 individuals with mild cognitive impairment (320 [53%] were female) were classified into 8 A±/T±/N± categories according to the abnormal (+)/normal (-) status of Aβ (18F-florbetapir or 18F-florbetaben) positron emission tomography (PET), 18F-flortaucipir PET, and adjusted hippocampal volume (aHCV). Follow-up Aβ PET, tau PET, and aHCV measurements at 0.6 to 4.1 years were available for 35% to 63% of the sample. Baseline Aβ, tau, and aHCV were compared between different A/T/N profiles. We investigated the associations of baseline and longitudinal Aβ, tau, and neurodegeneration in relation to one another continuously. RESULTS: Among T- participants, tau was higher for A+/T-/N- individuals compared with the A-/T-/N- group (p = .02). Among N- participants, neurodegeneration was worse among A+/T+/N- individuals compared with the A-/T-/N- group (p = .001). High baseline Aβ was associated (p < .001) with subsequent tau increase and high baseline tau was associated (p = .002) with subsequent aHCV decrease, whereas high tau and low aHCV at baseline were not associated with subsequent Aβ increase. CONCLUSIONS: These findings define a sequence of pathological events in Alzheimer's disease that support a current model of Alzheimer's disease pathogenesis in which Aβ appears early, followed by deposition of abnormal tau aggregates and subsequent neurodegeneration.
BACKGROUND: Amyloid-β (Aβ) likely plays a primary role in Alzheimer's disease pathogenesis, but longitudinal Aβ, tau, and neurodegeneration (A/T/N) measurements in the same individuals have rarely been examined to verify the temporal dynamics of these biomarkers. METHODS: In this study, we investigated the temporal ordering of Aβ, tau, and neurodegeneration using longitudinal biomarkers in nondemented elderly individuals. A total of 395 cognitively unimpaired individuals and 204 individuals with mild cognitive impairment (320 [53%] were female) were classified into 8 A±/T±/N± categories according to the abnormal (+)/normal (-) status of Aβ (18F-florbetapir or 18F-florbetaben) positron emission tomography (PET), 18F-flortaucipir PET, and adjusted hippocampal volume (aHCV). Follow-up Aβ PET, tau PET, and aHCV measurements at 0.6 to 4.1 years were available for 35% to 63% of the sample. Baseline Aβ, tau, and aHCV were compared between different A/T/N profiles. We investigated the associations of baseline and longitudinal Aβ, tau, and neurodegeneration in relation to one another continuously. RESULTS: Among T- participants, tau was higher for A+/T-/N- individuals compared with the A-/T-/N- group (p = .02). Among N- participants, neurodegeneration was worse among A+/T+/N- individuals compared with the A-/T-/N- group (p = .001). High baseline Aβ was associated (p < .001) with subsequent tau increase and high baseline tau was associated (p = .002) with subsequent aHCV decrease, whereas high tau and low aHCV at baseline were not associated with subsequent Aβ increase. CONCLUSIONS: These findings define a sequence of pathological events in Alzheimer's disease that support a current model of Alzheimer's disease pathogenesis in which Aβ appears early, followed by deposition of abnormal tau aggregates and subsequent neurodegeneration.
Authors: Zonghua Li; Michael G Heckman; Takahisa Kanekiyo; Yuka A Martens; Gregory S Day; Maria Vassilaki; Chia-Chen Liu; David A Bennett; Ronald C Petersen; Na Zhao; Guojun Bu Journal: Neurology Date: 2022-03-21 Impact factor: 11.800
Authors: Christina B Young; Susan M Landau; Theresa M Harrison; Kathleen L Poston; Elizabeth C Mormino Journal: Neuroimage Date: 2021-09-03 Impact factor: 6.556
Authors: Christopher J Weber; Maria C Carrillo; William Jagust; Clifford R Jack; Leslie M Shaw; John Q Trojanowski; Andrew J Saykin; Laurel A Beckett; Cyrille Sur; Naren P Rao; Patricio Chrem Mendez; Sandra E Black; Kuncheng Li; Takeshi Iwatsubo; Chiung-Chih Chang; Ana Luisa Sosa; Christopher C Rowe; Richard J Perrin; John C Morris; Amanda M B Healan; Stephen E Hall; Michael W Weiner Journal: Alzheimers Dement (N Y) Date: 2021-12-31