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. 2024 Jul 23;16(1):164.
doi: 10.1186/s13195-024-01534-4.

Moderation of thyroid hormones for the relationship between amyloid and tau pathology

Jeong Hyeon Byeon  1 , Min Soo Byun  1   2 , Dahyun Yi  3 , Joon Hyung Jung  4 , Bo Kyung Sohn  5 , Yoon Young Chang  5 , Nayeong Kong  6 , Gijung Jung  3 , Hyejin Ahn  7 , Jun-Young Lee  2   8 , Yun-Sang Lee  9 , Yu Kyeong Kim  10 , Dong Young Lee  11   12   13   14 ; KBASE Research Group
Collaborators, Affiliations

Moderation of thyroid hormones for the relationship between amyloid and tau pathology

Jeong Hyeon Byeon et al. Alzheimers Res Ther. .

Abstract

Background: Altered thyroid hormone levels have been associated with increased risk of Alzheimer's disease (AD) dementia and related cognitive decline. However, the neuropathological substrates underlying the link between thyroid hormones and AD dementia are not yet fully understood. We first investigated the association between serum thyroid hormone levels and in vivo AD pathologies including both beta-amyloid (Aβ) and tau deposition measured by positron emission tomography (PET). Given the well-known relationship between Aβ and tau pathology in AD, we additionally examined the moderating effects of thyroid hormone levels on the association between Aβ and tau deposition.

Methods: This cross-sectional study was conducted as part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) cohort. This study included a total of 291 cognitively normal adults aged 55 to 90. All participants received comprehensive clinical assessments, measurements for serum total triiodothyronine (T3), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH), and brain imaging evaluations including [11C]-Pittsburgh compound B (PiB)- PET and [18F] AV-1451 PET.

Results: No associations were found between either thyroid hormones or TSH and Aβ and tau deposition on PET. However, fT4 (p = 0.002) and fT3 (p = 0.001) exhibited significant interactions with Aβ on tau deposition: The sensitivity analyses conducted after the removal of an outlier showed that the interaction effect between fT4 and Aβ deposition was not significant, whereas the interaction between fT3 and Aβ deposition remained significant. However, further subgroup analyses demonstrated a more pronounced positive relationship between Aβ and tau in both the higher fT4 and fT3 groups compared to the lower group, irrespective of outlier removal. Meanwhile, neither T3 nor TSH had any interaction with Aβ on tau deposition.

Conclusion: Our findings suggest that serum thyroid hormones may moderate the relationship between cerebral Aβ and tau pathology. Higher levels of serum thyroid hormones could potentially accelerate the Aβ-dependent tau deposition in the brain. Further replication studies in independent samples are needed to verify the current results.

Keywords: Alzheimer’s disease; Amyloid beta; Positron emission tomography; Tau; Thyroid hormone; Thyroid-stimulating hormone.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Moderating effects of thyroid hormones on the relationships between Aβ and tau deposition. Notes: To effectively demonstrate the moderating effects, participants were divided into two subgroups based on thyroid hormone levels. Each line represents a regression line for IT tau deposition, with global Aβ deposition as the independent variable, controlling for age, sex, and APOE ε4 positivity. The shaded regions demonstrate the 95% confidence intervals of the regression lines. Abbreviations: Aβ beta-amyloid, IT inferior temporal, SUVR standardized uptake value ratio, T3 triiodothyronine, T4 thyroxine, APOE Apolipoprotein E
See this image and copyright information in PMC

References

    1. Beydoun M, Beydoun H, Kitner-Triolo M, Kaufman J, Evans M, Zonderman A. Thyroid hormones are associated with cognitive function: moderation by sex, race, and depressive symptoms. J Clin Endocrinol Metab. 2013;98(8):3470–81. 10.1210/jc.2013-1813 - DOI - PMC - PubMed
    1. Smith JW, Evans AT, Costall B, Smythe JW. Thyroid hormones, brain function and cognition: a brief review. Neurosci Biobehav Rev. 2002;26(1):45–60. 10.1016/S0149-7634(01)00037-9 - DOI - PubMed
    1. Gan EH, Jagger C, Yadegarfar ME, Duncan R, Pearce SH. Changes in serum thyroid function predict cognitive decline in the very old: Longitudinal findings from the Newcastle 85+ study. Thyroid. 2021;31(8):1182–91. 10.1089/thy.2020.0596 - DOI - PubMed
    1. Tan ZS, Beiser A, Vasan RS, Au R, Auerbach S, Kiel DP, et al. Thyroid function and the risk of Alzheimer disease: the Framingham Study. Arch Intern Med. 2008;168(14):1514–20. 10.1001/archinte.168.14.1514 - DOI - PMC - PubMed
    1. Chaker L, Wolters FJ, Bos D, Korevaar TI, Hofman A, van der Lugt A, et al. Thyroid function and the risk of dementia: The Rotterdam Study. Neurology. 2016;87(16):1688–95. 10.1212/WNL.0000000000003227 - DOI - PubMed

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