Contributive Role of Hyperglycemia and Hypoglycemia Towards the Development of Alzheimer's Disease

Mol Neurobiol. 2022 Jul;59(7):4274-4291. doi: 10.1007/s12035-022-02846-y. Epub 2022 May 3.

Abstract

Alzheimer's disease (AD) is one of the causes of dementia that results from several infections/biological conditions leading to either cell disruption or loss of neuronal communication. Studies have documented the accumulation of two proteins, beta-amyloid (Aβ), which accumulates on the exteriors of neurons, and tau (Tau), which assembles at the interiors of brain cells and is chiefly liable for the progression of the disease. Several molecular and cellular pathways account for the accumulation of amyloid-β and the formation of neurofibrillary tangles, which are phosphorylated variants of Tau protein. Moreover, research has revealed a potential connection between AD and diabetes. It has also been demonstrated that both hypoglycemia and hyperglycemia have a significant role in the development of AD. In addition, SUMO (small ubiquitin-like modifier protein) plays a crucial role in the pathogenesis of AD. SUMOylation is the process by which modification of amyloid precursor protein (APP) and Tau takes place. Furthermore, Drosophila melanogaster has proven to be an efficient model organism in studies to establish the relationship between AD and variations in blood glucose levels. In addition, the review successfully identifies the common pathway that links the effects of fluctuations in glucose levels on AD pathogenesis and advancements.

Keywords: Alzheimer’s disease; Amyloid Precursor Protein; Hyperglycemia; Hypoglycemia; SUMOylation of APP and Tau protein.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / metabolism
  • Animals
  • Drosophila melanogaster / metabolism
  • Hyperglycemia* / complications
  • Hypoglycemia* / complications
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • tau Proteins