TYPE 2 DIABETES AND ALZHEIMER'S
ONE STONE, TWO BIRDS?
Scientists make a breakthrough in the search for the cure of Alzheimer's
“In the latter stage of the disease, most of the brain cortex is seriously damaged. The brain shrinks dramatically due to widespread cell death. Individuals lose their ability to communicate, to recognize family and loved ones and to care for themselves.”
Alzheimer’s disease, a neurodegenerative disease often suffered by the aged has become an ailment needing urgently, a cure or preventive treatment. In 2017, it was recorded that the disease affected 500,000 people worldwide who were below the age of 65 (Alzheimer's Association, 2017). The disease which was discovered by and named after Dr. Alois Alzheimer in 1906 when he noticed changes in the brain tissue of a woman who died of a rare kind of mental illness is characterized by brain cell death which begins with the death of neurons and further, the malfunctioning of the synapse (Alzheimer’s
What causes this in Alzheimer’s is quite unknown. However, research has shown that people diagnosed with Alzheimer’s often have certain plaques and tangles found in their brains.
Does the word plaque ring a bell in your mind?
Imagine instead a mess made from clustered glue or any other sticky substance.
So plaques like that gather in the brain of an Alzheimer’s sufferer; these plaques are made from Beta Amyloid proteins normally found around neurons. These proteins form clusters and block cell to cell synapsing.
The brain of a patient with
These discoveries- although they point us towards the cause of this quite dangerous disease- have led us to a T junction where we are unsure which way to go. While drugs which help inhibit
These scientists, being forearmed with the knowledge that people who have Type 2 diabetes (High blood glucose) generally are at a risk of having Alzheimer’s (Research even says a
If you’re wondering what the link is between Diabetes and Alzheimer’s, quit wondering. I got you.
In 2015, Moran et al performed and published a research on the correlation of Alzheimer’s with Diabetes. They selected 120 aging adults who had Type 2 diabetes and 700 who didn’t. Their cerebrospinal fluids were collected. Basically, a fluid found in the brain and spinal cord. Tests were run on this fluid alongside MRI scans just to measure the amount of Tau and
A further pointer to this relation is the fact that people with type 2 diabetes generally have more insulin in their bodies because of their cells’ resistance to insulin and the body’s attempt to produce more insulin to match the blood sugar level. This high level of insulin has been discovered to pose harm to the brain and may be responsible for the formation of the tangles and plaques. (Sauer, 2016)
That settled. What did the scientists do?
They sought to see the effect of a novel drug called triple receptor agonist (TA) originally discovered for the treatment of diabetes on an Alzheimer’s disease brain. This triple agonist drug is said to be able to activate three different hormone receptors. They include glucagon(GCG), glucagon-like peptide-1(GLP1) and glucose-dependent insulinotropic polypeptide(
Hold on. Let’s understand the jargon.
A receptor is generally activated by certain hormones. GCG, GLP1
This TA which already had acquired a name as a result of its previously attained feat was given to a transgenic mouse model of Alzheimer’s, specifically an APP/PS1 model.
I got you again.
What this means is that the mouse used was transduced with human transgenes containing certain mutations on the Amyloid Precursor Protein(APP) gene- Amyloid rings a bell, yeah?- and the presenilin1 (PS1) gene both on chromosomes 21 and 14 respectively. By transgenesis, Alzheimer’s was stimulated in the brain of the mouse and this drug was given to the mice at 10nmol/kg for two months. After which, the results were profound. In the words of JingJing Tai and the other researchers in their 2017 published paper,
"The results showed that treatment with TA significantly reversed the memory deficit in the APP/PS1 mice in a spatial water maze test."
"The drug reduced levels of the mitochondrial pro-apoptotic signaling molecule
BAX,increased the anti-apoptotic signaling molecule Bcl-2. (Apoptosis= cell death so pro apoptosis basically enhances cell death while anti-apoptosis does the opposite)"
"It further enhanced the levels of BDNF, a key growth factor that protects synaptic function. Levels of synaptophysin were enhanced, demonstrating protection from synaptic loss that is observed in
"Furthermore, TA treatment reduced the total amount of β-amyloid, reduced
neuro-inflammationand oxidative stress in the cortex and hippocampus."
So there! If a transgenic model of
A potential side effect of the drug is reduced appetite which would normally translate to weight loss as one of the triple agonist hormones GLP-1 has been known to promote satiety and therefore reduce food and water intake. However, this is a small price to pay in the face of the potential victory of obtaining a cure for Alzheimer’s, a disease which claims the lives of its patients within an average of eight years.
For the family and friends of AD sufferers, this is great news. The thought of recovery, of renewed cognitive abilities, of maybe impaired speech being
Finan, B., Yang, B., Ottaway, N., Smiley, D.L., Ma, T., Clemmensen, C., Chabenne, J., Zhang, L., Habegger, K.M., Fischer, K., Campbell, J.E., Sandoval, D., Seeley, R.J., Bleicher, K., Uhles, S., Riboulet, W., Funk, J., Hertel, C., Belli, S., Sebokova, E., Conde-Knape, K., Konkar, A., Drucker, D.J., Gelfanov, V., Pfluger, P.T., Muller, T.D., Perez-Tilve, D., DiMarchi, R.D., Tschop, M.H., 2015. A rationally designed monomeric peptide
Moran C, Beare, R, Phan, T.G, Bruce, D.G,
Tai, J., Liu, W., Li, Y., Li, L., Hölscher, C. 2017. Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer’s disease.
Sauer, A. 2016. How Alzheimer’s could be type 2 diabetes. Alzheimers.net URL: https://www.alzheimers.net/2015-10-14/how-alzheimers-could-be-type-2-diabetes/
Alzheimer’s Association. 2016 Alzheimer’s Disease Facts and Figures. Alzheimer’s & Dementia 2016;12(4) URL: https://www.alz.org/documents_custom/2016-facts-and-figures.pdf
Written by Ibiagbani Mercy Max-Harry for African Biosciences Blog.