Poster No:
263
Submission Type:
Abstract Submission
Authors:
TAO GUO1, Yumi Takano1,2, Yasuko Tatewaki1,2, Ye Zhang1, Naoki Naoki Tomita1,2, Michiho Muranaka1,2, Taizen Nakase1,2, Yasuyuki Taki1,2,3
Institutions:
1Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer, Tohoku University, Aoba-ku, Sendai 980-8575, Japan, 2Department of Geriatric Medicine and Neuroimaging, Tohoku University Hospital, Aoba-ku, Sendai 980-8575, Japan, 3Smart-Aging Research Center, Tohoku University, Aoba-ku, Sendai 980-8575, Japan
First Author:
TAO GUO
Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer
Tohoku University, Aoba-ku, Sendai 980-8575, Japan
Co-Author(s):
Yumi Takano
Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer|Department of Geriatric Medicine and Neuroimaging, Tohoku University Hospital
Tohoku University, Aoba-ku, Sendai 980-8575, Japan|Aoba-ku, Sendai 980-8575, Japan
Yasuko Tatewaki
Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer|Department of Geriatric Medicine and Neuroimaging, Tohoku University Hospital
Tohoku University, Aoba-ku, Sendai 980-8575, Japan|Aoba-ku, Sendai 980-8575, Japan
Ye Zhang
Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer
Tohoku University, Aoba-ku, Sendai 980-8575, Japan
Naoki Naoki Tomita
Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer|Department of Geriatric Medicine and Neuroimaging, Tohoku University Hospital
Tohoku University, Aoba-ku, Sendai 980-8575, Japan|Aoba-ku, Sendai 980-8575, Japan
Michiho Muranaka
Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer|Department of Geriatric Medicine and Neuroimaging, Tohoku University Hospital
Tohoku University, Aoba-ku, Sendai 980-8575, Japan|Aoba-ku, Sendai 980-8575, Japan
Taizen Nakase
Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer|Department of Geriatric Medicine and Neuroimaging, Tohoku University Hospital
Tohoku University, Aoba-ku, Sendai 980-8575, Japan|Aoba-ku, Sendai 980-8575, Japan
Yasuyuki Taki
Department of Aging Research and Geriatric Medicine, Institute of Development, Aging and Cancer|Department of Geriatric Medicine and Neuroimaging, Tohoku University Hospital|Smart-Aging Research Center, Tohoku University
Tohoku University, Aoba-ku, Sendai 980-8575, Japan|Aoba-ku, Sendai 980-8575, Japan|Aoba-ku, Sendai 980-8575, Japan
Introduction:
Calcium is considered involved in the pathophysiology of cognitive decline and Alzheimer's disease (AD)1.
According to the calcium hypothesis of AD2, the amyloidogenic pathway may function to remodel the neuronal Ca2+ signaling pathways responsible for cognition. This remodeling calcium signaling can disrupt the synaptic strength, and the increased calcium concentration can trigger apoptosis, resulting in severe cognitive decline and neuronal cell death. Previous studies have showed that serum Ca2+ can easily cross the blood-brain barrier3. High extracellular calcium levels may enhance calcium influx in neurons during signaling when calcium channels open, leading to calcium overload and neuronal death4.
Current studies reported that higher serum calcium status (even if not hypercalcemia) may increase the risk of AD in elders. Serum calcium is a useful biomarker in predicting clinical progression in nondemented elders5.
However, the potential mechanism of serum calcium as a biomarker for AD remains unclear. In our study, we aimed to investigate the relationship between serum calcium and AD by using voxel-based morphometry (VBM) based regional gray matter volume (rGMV) to visualize brain alterations associated with calcium.
Methods:
The sample was derived from our memory clinic in Tohoku University Hospital, which included 76 patients (age range from 50 years to 93 years). The patients had brain MRI scans completed at the investigation. We also collected the patients' age, gender, years of education, mini-mental state examination score (MMSE), and blood test results. The exclusion criteria for all participants were: (1) other neurological disorders; and (2) severe medical conditions or terminal diseases that may influence the results of imaging studies.
MRI scanner was used to acquire a 3D T1-weighted structural image. Pre-processing of structural images was performed using Statistical Parametric Mapping software (SPM12) implemented in MATLAB. We used SPM12 to conduct a whole-brain multiple regression analysis to examine the association between serum calcium level and rGMV on brain structure. The subjects' age, gender, total brain volume (TBV), years of education and MMSE score were entered as covariates of no interest in these analyses.
Results:
After adjusting for age, gender, TBV, years of education and MMSE scores we found increased serum calcium level was significantly associated with decreased rGMV in the bilateral fusiform gyrus (Left: MNI coordinates at peak voxel = (-34, -38, -12); t = 5.48, pFWE = 0.002, cluster size = 1701. Right: MNI coordinates at peak voxel = (36, -38, -10); t = 4.62, pFWE = 0.008, cluster size = 1217).
Conclusions:
In the present study, we found serum calcium was negatively correlated with rGMV in the bilateral fusiform gyrus after adjusting for covariates.
The fusiform gyrus, a brain region that plays roles in vision for perception, object recognition, and reading, has gained attention in epigenetic studies6. It has been reported that specific changes in functional connectivity of the fusiform gyrus in MCI, considered a risk factor of conversion to AD, and atrophy of the fusiform gyrus occur as a consequence of amyloid load within the hippocampus. Thus, the fusiform gyrus has been identified as a critical brain region associated with MCI, which may increase the risk of AD development7. In fusiform gyrus, Transmembrane O-Mannosyltransferase Targeting Cadherins 2 (TMTC2) is a novel candidate gene that is identified co-expressed in AD, and this gene is also involved in endoplasmic reticulum (ER) calcium homeostasis7. However, the molecular mechanism between serum calcium levels and fusiform gyrus remains to be studied.
Our study suggests that a potential association between serum calcium levels and brain structural alterations, indicating that serum calcium may serve as a useful biomarker in clinical AD patients.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Lifespan Development:
Aging
Novel Imaging Acquisition Methods:
Anatomical MRI 2
Keywords:
Degenerative Disease
MRI
Other - Serum Calcium; Alzheimer's Disease; Voxel-based morphometry (VBM)
1|2Indicates the priority used for review
Provide references using author date format
1. Bussiere R. Upregulation of the Sarco-Endoplasmic Reticulum Calcium ATPase 1 Truncated Isoform Plays a Pathogenic Role in Alzheimer's Disease. Cells. 2019 Nov 28;8(12):1539.
2. Berridge M J. Calcium hypothesis of Alzheimer’s disease[J]. Pflügers Archiv-European Journal of Physiology, 2010, 459: 441-449.
3. Yarlagadda A. Blood brain barrier: the role of calcium homeostasis. Psychiatry (Edgmont). 2007 Dec;4(12):55-9.
4. Toescu EC. Ca2+ regulation and gene expression in normal brain aging Trends. Neurosci 27:614620.
5. Ma LZ. Serum Calcium Predicts Cognitive Decline and Clinical Progression of Alzheimer's Disease. Neurotox Res. 2021 Jun;39(3):609-617.
6. Srinivasan K. Alzheimer's Patient Microglia Exhibit Enhanced Aging and Unique Transcriptional Activation. Cell Rep. 2020 Jun 30;31(13):107843.
7. Ma, D. The fusiform gyrus exhibits an epigenetic signature for Alzheimer’s disease. Clin Epigenet 12, 129 (2020).