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Diabetic and non-diabetic Alzheimer’s disease: studying mitochondria in post-mortem brain to understand the underlying mechanisms

Diabetes can increase the risk of Alzheimer's disease (AD) through unknown mechanisms. Mitochondria are cellular organelles which produce energy and contain an extranuclear genome known as mitochondrial DNA (mtDNA), a 16.5kb circular DS DNA molecule which codes for part of the cell's energy apparatus. The brain has high energy needs, using >20 % of the bodies' energy despite being <2% of weight, and can contain up to hundreds of thousands of mtDNA copies per cell.

Damage to mtDNA can result in defects in energy production. Previous research from our lab , using post-mortem material, found evidence of mtDNA changes and mitochondrial dysfunction in the parietal cortex from AD patients, and different patterns of mtDNA changes were seen when comparing the impact of AD alone versus AD and diabetes.

In the current project, we are testing the theory that energy deficiency in specific regions of human brain, caused by damage to mtDNA, may be one of the mechanisms contributing to AD pathogenesis. Further, we aim to determine whether damage to mitochondria takes place via different pathways in diabetic and non-diabetic AD.

The project will investigate disease associated changes in specific regions of the human brain as follows:

  1. Changes in mtDNA-copy number will be determined using absolute quantification.
  2. Damage to mtDNA (mtDNA heteroplasmy/mutations) will be identified using next generation sequencing.
  3. Changes in mitochondrial function and cell types changes will be evaluated using an array of molecular biology techniques (mRNA expression using qPCR, protein changes using Western blotting, quadruple immunofluorescence, laser microdissection and immunohistochemical staining).
malik project8
Project status: Ongoing

Principal Investigators



Funding Body: Alzheimer’s Research UK

Amount: Interdisciplinary Research Grant from Alzheimer’s Research UK

Period: May 2022 - May 2025