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Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer’s dementia

Byman, Elin LU ; Nägga, Katarina LU ; Gustavsson, Anna Märta LU ; Andersson-Assarsson, Johanna ; Hansson, Oskar LU orcid ; Sonestedt, Emily LU orcid and Wennström, Malin LU (2020) In Alzheimer's Research and Therapy 12(1).
Abstract

Background: Previous studies have shown that copy number variation (CNV) in the alpha (α)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer’s dementia (AD). We have previously demonstrated the presence of α-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients. In the current study, we investigate the relationship between AMY1A copy number and AD, memory performance, and brain α-amylase activity. Methods and materials: The association between AMY1A copy number and development of AD was analyzed in 5422 individuals (mean age at baseline 57.5 ± 5.9, females 58.2%) from the Malmö diet and cancer study... (More)

Background: Previous studies have shown that copy number variation (CNV) in the alpha (α)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer’s dementia (AD). We have previously demonstrated the presence of α-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients. In the current study, we investigate the relationship between AMY1A copy number and AD, memory performance, and brain α-amylase activity. Methods and materials: The association between AMY1A copy number and development of AD was analyzed in 5422 individuals (mean age at baseline 57.5 ± 5.9, females 58.2%) from the Malmö diet and cancer study genotyped for AMY1A copy number, whereof 247 where diagnosed with AD during a mean follow-up of 20 years. Associations between AMY1A copy number and cognitive performance where analyzed in 791 individuals (mean age at baseline 54.7 ± 6.3, females 63%), who performed Montreal Cognitive Assessment (MoCA) test. Correlation analysis between α-amylase activity or α-amylase gene expression and AMY1A copy number in post-mortem hippocampal tissue from on demented controls (n = 8) and AD patients (n = 10) was also performed. Results: Individuals with very high (≥10) AMY1A copy number had a significantly lower hazard ratio of AD (HR = 0.62, 95% CI 0.41–0.94) and performed significantly better on MoCA delayed word recall test, compared to the reference group with AMY1A copy number 6. A trend to lower hazard ratio of AD was also found among individuals with low AMY1A copy number (1–5) (HR = 0.74, 95% CI 0.53–1.02). A tendency towards a positive correlation between brain α-amylase activity and AMY1A copy number was found, and females showed higher brain α-amylase activity compared to males. Conclusion: Our study suggests that the degree of α-amylase activity in the brain is affected by AMY1A copy number and gender, in addition to AD pathology. The study further suggests that very high AMY1A copy number is associated with a decreased hazard ratio of AD and we speculate that this effect is mediated via a beneficial impact of AMY1A copy number on episodic memory performance.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, DNA copy number variation, Gender, Human brain, Memory, Montreal cognitive assessment, Salivary alpha amylases
in
Alzheimer's Research and Therapy
volume
12
issue
1
article number
158
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85096398484
  • pmid:33220711
ISSN
1758-9193
DOI
10.1186/s13195-020-00726-y
language
English
LU publication?
yes
id
62e51313-b8d6-4246-98c3-988de2544da8
date added to LUP
2020-11-30 11:14:03
date last changed
2022-09-24 18:13:09
@article{62e51313-b8d6-4246-98c3-988de2544da8,
  abstract     = {{<p>Background: Previous studies have shown that copy number variation (CNV) in the alpha (α)-amylase gene (AMY1A) is associated with body mass index, insulin resistance, and blood glucose levels, factors also shown to increase the risk of Alzheimer’s dementia (AD). We have previously demonstrated the presence of α-amylase in healthy neuronal dendritic spines and a reduction of the same in AD patients. In the current study, we investigate the relationship between AMY1A copy number and AD, memory performance, and brain α-amylase activity. Methods and materials: The association between AMY1A copy number and development of AD was analyzed in 5422 individuals (mean age at baseline 57.5 ± 5.9, females 58.2%) from the Malmö diet and cancer study genotyped for AMY1A copy number, whereof 247 where diagnosed with AD during a mean follow-up of 20 years. Associations between AMY1A copy number and cognitive performance where analyzed in 791 individuals (mean age at baseline 54.7 ± 6.3, females 63%), who performed Montreal Cognitive Assessment (MoCA) test. Correlation analysis between α-amylase activity or α-amylase gene expression and AMY1A copy number in post-mortem hippocampal tissue from on demented controls (n = 8) and AD patients (n = 10) was also performed. Results: Individuals with very high (≥10) AMY1A copy number had a significantly lower hazard ratio of AD (HR = 0.62, 95% CI 0.41–0.94) and performed significantly better on MoCA delayed word recall test, compared to the reference group with AMY1A copy number 6. A trend to lower hazard ratio of AD was also found among individuals with low AMY1A copy number (1–5) (HR = 0.74, 95% CI 0.53–1.02). A tendency towards a positive correlation between brain α-amylase activity and AMY1A copy number was found, and females showed higher brain α-amylase activity compared to males. Conclusion: Our study suggests that the degree of α-amylase activity in the brain is affected by AMY1A copy number and gender, in addition to AD pathology. The study further suggests that very high AMY1A copy number is associated with a decreased hazard ratio of AD and we speculate that this effect is mediated via a beneficial impact of AMY1A copy number on episodic memory performance.</p>}},
  author       = {{Byman, Elin and Nägga, Katarina and Gustavsson, Anna Märta and Andersson-Assarsson, Johanna and Hansson, Oskar and Sonestedt, Emily and Wennström, Malin}},
  issn         = {{1758-9193}},
  keywords     = {{Alzheimer’s disease; DNA copy number variation; Gender; Human brain; Memory; Montreal cognitive assessment; Salivary alpha amylases}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Alzheimer's Research and Therapy}},
  title        = {{Alpha-amylase 1A copy number variants and the association with memory performance and Alzheimer’s dementia}},
  url          = {{http://dx.doi.org/10.1186/s13195-020-00726-y}},
  doi          = {{10.1186/s13195-020-00726-y}},
  volume       = {{12}},
  year         = {{2020}},
}