Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov;47(12):2879-2886.
doi: 10.1007/s00259-020-04773-3. Epub 2020 Apr 29.

Temporal trajectories of in vivo tau and amyloid-β accumulation in Alzheimer's disease

Min Seok Baek #  1 , Hanna Cho #  1 , Hye Sun Lee  2 , Jae Yong Choi  3   4 , Jae Hoon Lee  3 , Young Hoon Ryu  5 , Myung Sik Lee  1 , Chul Hyoung Lyoo  6
Affiliations

Temporal trajectories of in vivo tau and amyloid-β accumulation in Alzheimer's disease

Min Seok Baek et al. Eur J Nucl Med Mol Imaging. 2020 Nov.

Abstract

Purpose: To investigate the temporal trajectories of tau and amyloid-β (Aβ) accumulation in Alzheimer's disease (AD) by using the longitudinal positron emission tomography (PET) study.

Methods: A total of 132 participants, who were healthy volunteers or recruited in our memory disorder clinic, completed longitudinal 18F-flortaucipir and 18F-florbetaben PET studies with a mean follow-up time of 2 years. Referencing baseline data from 57 Aβ-negative cognitively unimpaired individuals, Z-scores and their annual changes were calculated with the global cortical or regional standardized uptake value ratios measured at baseline and follow-up after correcting for partial volume effect. The temporal trajectories of tau and Aβ burden as a function of time were obtained based on the spline models from the annual changes and baseline Z-score data.

Results: Tau burden first emerged in the Braak's stage I-II regions, followed by stage III-IV regions, and finally in the stage V-VI regions. Time intervals between two time points at which Z-score curves rose above 2 were 17.3 years for the stages I-II and III-IV and 15.2 years for the stages III-IV and V-VI. Rise in the tau curve for stages I-II preceded that for global cortical Aβ, while the rise in global cortical Aβ curve preceded that for global cortical tau. Aβ accumulation rate was attenuated during the surge in tau burden in the global cortex and reached a plateau.

Conclusion: Sequential appearance of Aβ and tau accumulation supports a hypothetical dynamic biomarker model and Braak's hierarchical tau spreading model in AD.

Keywords: 18F-flortaucipir; Alzheimer’s disease; Positron emission tomography; Tau.

PubMed Disclaimer

References

    1. Ingelsson M, Fukumoto H, Newell KL, Growdon JH, Hedley-Whyte ET, Frosch MP, et al. Early Abeta accumulation and progressive synaptic loss, gliosis, and tangle formation in AD brain. Neurology. 2004;62:925–31. - DOI
    1. Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR. Neuropathologic substrate of mild cognitive impairment. Arch Neurol. 2006;63:38–46. - DOI
    1. Tapiola T, Alafuzoff I, Herukka SK, Parkkinen L, Hartikainen P, Soininen H, et al. Cerebrospinal fluid {beta}-amyloid 42 and tau proteins as biomarkers of Alzheimer-type pathologic changes in the brain. Arch Neurol. 2009;66:382–9. - DOI
    1. Buchhave P, Minthon L, Zetterberg H, Wallin AK, Blennow K, Hansson O. Cerebrospinal fluid levels of beta-amyloid 1-42, but not of tau, are fully changed already 5 to 10 years before the onset of Alzheimer dementia. Arch Gen Psychiatry. 2012;69:98–106. - DOI
    1. Caroli A, Frisoni GB. Alzheimer's disease neuroimaging I. The dynamics of Alzheimer's disease biomarkers in the Alzheimer's disease neuroimaging initiative cohort. Neurobiol Aging. 2010;31:1263–74. - DOI

Publication types

LinkOut - more resources