Metals toxicity and its correlation with the gene expression in Alzheimer's disease

Mol Biol Rep. 2021 Apr;48(4):3245-3252. doi: 10.1007/s11033-021-06386-x. Epub 2021 May 10.

Abstract

Alzheimer's disease is a common neurodegenerative disease in the elderly population and a leading cause of dementia. Genetics and environmental risk factors were considered to play a major role in the onset of the disease. This study aimed to examine the correlation between different metals levels and the gene expression in Alzheimer's patients with age-matched control subjects. Non- essential metals were measured in the whole blood due to its higher concentration in red blood corpuscles (RBCs) and essential biometals in the serum samples of Alzheimer's disease (AD) by using Inductively coupled plasma optical emission spectroscopy (ICP-OES) that allows the analysis and detection of the different elements at low levels. Gene expression level was performed by quantitative real-time PCR (qRT-PCR). In this study, the levels of Lead and Arsenic metals were not detected in the AD patient samples. Cadmium, Mercury, and Aluminum were found higher in cases as compared to controls with 0.009240 ± 0.0007707 (P = < 0.0001), 0.02332 ± 0.001041 (P = < 0.0001), and 0.09222 ± 0.02804 (P = 0.0087) respectively. Essential biometal like copper was higher 0.1274 ± 0.02453 (P = 0.0254) in cases, while iron 0.1117 ± 0.009599 (P = 0.0304) and zinc 0.03800 ± 0.003462 mg/L were found significantly lower as compared to controls. All targeted genes such as APP, PSEN1, PSEN2, and APOE4 were found up-regulated in AD patients. We concluded that there was no significant correlation between metals dyshomeostasis and gene expressions in this study.

Keywords: Alzheimer's disease; Amyloid-beta plaque; Apolipoprotein; Gene expression; Neurodegenerative disease; Non- essential metals.

MeSH terms

  • Aged
  • Aluminum / blood
  • Alzheimer Disease / metabolism*
  • Apolipoproteins / genetics
  • Apolipoproteins / metabolism
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Cadmium / blood
  • Copper / blood
  • Female
  • Gene Expression*
  • Humans
  • Iron / blood
  • Male
  • Metals / blood*
  • Neurodegenerative Diseases / metabolism
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Presenilin-2 / genetics
  • Presenilin-2 / metabolism
  • Zinc / blood

Substances

  • Apolipoproteins
  • Apolipoproteins E
  • Metals
  • PSEN1 protein, human
  • Presenilin-1
  • Presenilin-2
  • Cadmium
  • Copper
  • Aluminum
  • Iron
  • Zinc