Abstract
BackgroundThe present study investigated the relationships between thyroid hormone serum levels or thyroid-stimulating hormone (TSH) and two Alzheimer’s disease (AD)-specific biomarkers, cerebral amyloid beta (Aβ) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals.MethodsThis study assessed 148 CN individuals who received comprehensive clinical and neuropsychological assessments that included 11C-Pittsburgh Compound B (PiB)-positron emission tomography (PET) scans, 18F-deoxyglucose (FDG)-PET scans, and the quantification of serum triiodothyronine (T3), free T3, free thyroxine (fT4), and TSH levels.ResultsAll participants were clinically euthyroid. Independent negative associations were found between serum fT4 levels and global cerebral Aβ deposition after controlling for the effects of age, gender, and the apolipoprotein E ε4 (APOEε4) genotype. Although serum TSH levels were not associated with global cerebral Aβ deposition, they had a significant negative association with glucose metabolism in the precuneus/posterior cingulate cortex after controlling for age, gender, and the APOEε4 genotype. No other thyroid hormones exhibited relationships with either brain Aβ burden or glucose metabolism.ConclusionsEven in a clinical euthyroid state, low serum fT4 and high serum TSH levels appear to be differentially associated with AD-specific brain changes.
Highlights
The present study investigated the relationships between thyroid hormone serum levels or thyroid-stimulating hormone (TSH) and two Alzheimer’s disease (AD)-specific biomarkers, cerebral amyloid beta (Aβ) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals
All participants were clinically euthyroid but subclinical thyroid problems were found in 12 individuals (8.1%); of these 12 participants, nine had high TSH levels and three had low TSH levels
Exploratory univariate analyses In the exploratory step of the analyses using Pearson’s correlation, we found that the associations between serum Free thyroxine (fT4) and global cerebral Amyloid beta (Aβ) deposition, as well as between TSH and Cerebral glucose metabolism (CMglu) in the AD-signature region, are below the threshold (p < 0.1) (Additional file 1: Table S1)
Summary
The present study investigated the relationships between thyroid hormone serum levels or thyroid-stimulating hormone (TSH) and two Alzheimer’s disease (AD)-specific biomarkers, cerebral amyloid beta (Aβ) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals. Whether serum levels of thyroid hormones are associated with AD pathologies, such as cerebral amyloid beta protein (Aβ) deposition and neurodegeneration, in the living human brain remains unclear. Two pathological studies of postmortem human brain tissues showed that thyroid hormone levels and Aβ deposition are related [5, 10]. Detection of an association between thyroid hormone serum levels and cerebral Aβ deposition may be difficult in cognitively impaired individuals. It is important to investigate the relationships of thyroid hormones in serum with
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