Dataset Information

Associations of thyroid hormone serum levels with in-vivo Alzheimer's disease pathologies.

ABSTRACT:

Background

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 (A?) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals.

Methods

This 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.

Results

All participants were clinically euthyroid. Independent negative associations were found between serum fT4 levels and global cerebral A? deposition after controlling for the effects of age, gender, and the apolipoprotein E ?4 (APOE?4) genotype. Although serum TSH levels were not associated with global cerebral A? deposition, they had a significant negative association with glucose metabolism in the precuneus/posterior cingulate cortex after controlling for age, gender, and the APOE?4 genotype. No other thyroid hormones exhibited relationships with either brain A? burden or glucose metabolism.

Conclusions

Even in a clinical euthyroid state, low serum fT4 and high serum TSH levels appear to be differentially associated with AD-specific brain changes.

SUBMITTER: Choi HJ

PROVIDER: S-EPMC5561599 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Associations of thyroid hormone serum levels with in-vivo Alzheimer's disease pathologies.

Choi Hyo Jung HJ Byun Min Soo MS Yi Dahyun D Sohn Bo Kyung BK Lee Jun Ho JH Lee Jun-Young JY Kim Yu Kyung YK Lee Dong Young DY

Alzheimer's research & therapy 20170817 1

<h4>Background</h4>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.<h4>Methods</h4>This study assessed 148 CN individuals who received comprehensive clinical and neuropsychological assessments that included <sup>11</sup>C- ...[more]

PMID: 28818092

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Project description:IntroductionAlthough the heritability of sporadic Alzheimer's disease (AD) is estimated to be 60-80%, addressing the genetic contribution to AD risk still remains elusive. More specifically, it remains unclear whether genetic variants are able to affect neurodegenerative brain features that can be addressed by in vivo imaging techniques.MethodsTargeted sequencing analysis of the coding and UTR regions of 132 AD susceptibility genes was performed. Neuroimaging data using 11C-Pittsburgh Compound B positron emission tomography (PET), 18F-fluorodeoxyglucose PET, and MRI that are available from the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease) cohort were acquired. A total of 557 participants consisted of 336 cognitively normal (CN) adults, 137 mild cognitive impairment (MCI), and 84 AD dementia (ADD) groups.ResultsWe called 5391 high-quality single nucleotide variants (SNVs) on AD susceptibility genes and selected significant associations between variants and five in vivo AD pathologies: (1) amyloid β (Aβ) deposition, (2) AD-signature region cerebral glucose metabolism (AD-Cm), (3) posterior cingulate cortex (PCC) cerebral glucose metabolism (PCC-Cm), (4) AD-signature region cortical thickness (AD-Ct), and (5) hippocampal volume (Hv). The association analysis for common variants (allele frequency (AF) > 0.05) yielded several novel loci associated with Aβ deposition (PIWIL1-rs10848087), AD-Cm (NME8-rs2722372 and PSEN2-rs75733498), AD-Ct (PSEN1-rs7523) and, Hv (CASS4-rs3746625). Meanwhile, in a gene-based analysis for rare variants (AF < 0.05), cases carrying rare variants in LPL, FERMT2, NFAT5, DSG2, and ITPR1 displayed associations with the neuroimaging features. Exploratory voxel-based brain morphometry between the variant carriers and non-carriers was performed subsequently. Finally, we document a strong association of previously reported APOE variants with the in vivo AD pathologies and demonstrate that the variants exert a causal effect on AD susceptibility via neuroimaging features.ConclusionsThis study provides novel associations of genetic factors to Aβ accumulation and AD-related neurodegeneration to influence AD susceptibility.

Dataset Information

Associations of thyroid hormone serum levels with in-vivo Alzheimer's disease pathologies.

Background

Methods

Results

Conclusions

Publications

Associations of thyroid hormone serum levels with in-vivo Alzheimer's disease pathologies.

Similar Datasets

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