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A TREML2 missense variant influences specific hippocampal subfield volumes in cognitively normal elderly subjects.

ABSTRACT: INTRODUCTION:Triggering receptor expressed on myeloid cells-like transcript 2 gene (TREML2) is a newly identified AD susceptibility gene. Its missense variant rs3747742-C substantially decreases AD risk in both Caucasians and Han Chinese, but the underlying mechanisms remain elusive. In the present study, to uncover the possible mechanisms by which TREML2 rs3747742-C reduces AD risk, we investigated the possible relation of this variant with AD-related brain structures using a cognitively normal elderly population from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. METHODS:In total, 158 cognitively normal elders from ADNI database with complete data for brain structures and TREML2 rs3747742 genotype were included in this study. The association of TREML2 rs3747742 genotype with the structures of three cerebral cortices (entorhinal cortex, middle temporal gyrus, and parahippocampal gyrus), two subcortical regions (amygdala and hippocampus), and three subfields of hippocampus (CA1, CA2 + CA3, and CA4 + dentate gyrus) was investigated. RESULTS:A significant difference was noted in the volume of right CA1 subfield among three genotypes of TREML2 rs3747742 (p = .0364). In the multivariate analysis, TREML2 rs3747742-C significantly increased right CA1 subfield volume after adjusting for age, gender, education years, APOE ?4 status, and intracranial volume under the recessive genetic model (Bonferroni corrected p = .003586). CONCLUSION:The present study provides the first evidence that TREML2 rs3747742-C carriers have larger volumes of hippocampal CA1 subfield in a cognitively normal elderly population. These findings imply that enhancement of brain reserve may contribute to the protection of TREML2 rs3747742-C in AD susceptibility.

SUBMITTER: Wang SY

PROVIDER: S-EPMC7177563 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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A TREML2 missense variant influences specific hippocampal subfield volumes in cognitively normal elderly subjects.

Wang Si-Yu SY Xue Xiao X Duan Rui R Gong Peng-Yu PY E Yan Y Jiang Teng T Jiang Teng T Zhang Ying-Dong YD

Brain and behavior 20200219 4

<h4>Introduction</h4>Triggering receptor expressed on myeloid cells-like transcript 2 gene (TREML2) is a newly identified AD susceptibility gene. Its missense variant rs3747742-C substantially decreases AD risk in both Caucasians and Han Chinese, but the underlying mechanisms remain elusive. In the present study, to uncover the possible mechanisms by which TREML2 rs3747742-C reduces AD risk, we investigated the possible relation of this variant with AD-related brain structures using a cognitivel ...[more]

PMID: 32073739

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Project description:BackgroundThe human hippocampus comprises a number of interconnected histologically and functionally distinct subfields, which may be differentially influenced by cerebral pathology. Automated techniques are now available that estimate hippocampal subfield volumes using in vivo structural MRI data. To date, research investigating the influence of cerebral β-amyloid deposition-one of the earliest hypothesised changes in the pathophysiological continuum of Alzheimer's disease-on hippocampal subfield volumes in cognitively normal older individuals, has been limited.MethodsUsing cross-sectional data from 408 cognitively normal individuals born in mainland Britain (age range at time of assessment = 69.2-71.9 years) who underwent cognitive assessment, 18F-Florbetapir PET and structural MRI on the same 3 Tesla PET/MR unit (spatial resolution 1.1 x 1.1 x 1.1. mm), we investigated the influences of β-amyloid status, age at scan, and global white matter hyperintensity volume on: CA1, CA2/3, CA4, dentate gyrus, presubiculum and subiculum volumes, adjusting for sex and total intracranial volume.ResultsCompared to β-amyloid negative participants (n = 334), β-amyloid positive participants (n = 74) had lower volume of the presubiculum (3.4% smaller, p = 0.012). Despite an age range at scanning of just 2.7 years, older age at time of scanning was associated with lower CA1 (p = 0.007), CA4 (p = 0.004), dentate gyrus (p = 0.002), and subiculum (p = 0.035) volumes. There was no evidence that white matter hyperintensity volume was associated with any subfield volumes.ConclusionThese data provide evidence of differential associations in cognitively normal older adults between hippocampal subfield volumes and β-amyloid deposition and, increasing age at time of scan. The relatively selective effect of lower presubiculum volume in the β-amyloid positive group potentially suggest that the presubiculum may be an area of early and relatively specific volume loss in the pathophysiological continuum of Alzheimer's disease. Future work using higher resolution imaging will be key to exploring these findings further.

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A TREML2 missense variant influences specific hippocampal subfield volumes in cognitively normal elderly subjects.

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A TREML2 missense variant influences specific hippocampal subfield volumes in cognitively normal elderly subjects.

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