Study reveals a possible tie between the brain tangles associated with Alzheimer’s disease and type 2 diabetes

Tangles in your brain — never a good thing.

Tangles are dead and dying nerve cells that contain twisted strands of protein.

The presence of tangles, or tau proteins, in the brain is usually associated with Alzheimer’s disease.

The brain tissue of Alzheimer’s patients shows far fewer nerve cells and synapses than a healthy brain. In these cases, plaque — abnormal clusters of protein fragments — has built up between nerve cells.

Now, a study released today in the online version of Neurology, the official journal of the American Academy of Neurology, finds a possible connection between tangles and type 2 diabetes.

Read More: Get the Basics on Diabetes »

There is no evidence at this time that there is a cause-and-effect relationship between diabetes and the brain tangles.

According to Dr. Velandai Srikanth Ph.D., of Monash University in Melbourne, Australia, it has been known for some time that people with type 2 diabetes have double the risk of developing dementia.

Srikanth leads the multifaceted Stroke and Ageing Research group based in the Department of Medicine, School of Clinical Sciences, at Monash. He conceived the idea for the study, conducted the analysis and helped write the manuscript.

The study looked at the brain and spinal fluid of 816 people with an average age of 74. The results showed that 397 had mild cognitive impairment, which is often a precursor to dementia. Another 191 had Alzheimer’s disease dementia. The remaining 228 people displayed no problems with memory or thinking. In addition, 124 members of the overall group were diabetic.

“The finding of elevated tau protein in spinal fluid in people with diabetes has not been shown before” in living people, Srikanth told Healthline. “So this is a novel finding. However, we were surprised not to find a difference in brain amyloid levels between people with and without diabetes.”

The diabetics showed a reduced thickness of the cortex, the layer of the brain with the most nerve cells. Their cortical tissue was an average of 0.03 millimeters less than those who did not have diabetes, whether or not they had any impairment. The buildup of tangles may contribute to this loss of brain tissue.

Read More: Get the Facts on Alzheimer’s »

The study team defined its objective as determining whether type 2 diabetes mellitus influences neuro-degeneration in a manner similar to Alzheimer’s disease by promoting brain b-amyloid or tau.

In other words, what is the relationship among type 2 diabetes, the loss of brain cells and their connections, the levels of beta amyloid (a sticky buildup of plaques) and tau or tangles of protein in the spinal fluid of the participants?

The people in the study who had been diagnosed with diabetes had on average 16 picograms per milliliter more tau protein in their spinal and brain fluid whether or not they had received a diagnosis of dementia.

The findings were a bit of a surprise, Srikanth said.

“Brain amyloid build-up is often thought to underlie Alzheimer’s disease dementia,” he said. “We were expecting to see greater levels of amyloid in people with diabetes (which is a risk factor for Alzheimer’s disease dementia), but did not.”

Read More: The Difference Between Alzheimer’s and Dementia »

Dr. Cyrus Desouza, MBBS, an endocrinologist and professor of internal medicine at the University of Nebraska, discussed with Healthline several questions that need investigation to clarify the association between diabetes and dementia or cognitive decline.

  • “Does the duration, the degree of control, age of onset of diabetes or presence of other vascular disease contribute to the extent of cognitive impairment or dementia?
  • More importantly, if diabetes and co-morbid conditions are controlled appropriately, will this prevent or even reverse some of the changes seen in this study?
  • Do the multiple medications that diabetes patients take (such as statins) have anything to do with the cognitive decline or dementia?”

Srikanth also stressed the need for further study.

“This may just mean that our study was not large enough to pick [up] a small correlation,” he said. “Alternatively it may mean that tau protein pathways play a more important role (than amyloid) in diabetes-related nerve cell loss. One cannot also rule out a role for amyloid in initiating tau protein modification and tangle formation.”

Greater levels of tau in spinal fluid may reflect a greater build-up of tangles in the brain. These tangles may eventually contribute to the development of dementia.

Desouza agrees this work adds to the existing literature in this area, but as a small cross-sectional study, it has limitations.

“It highlights the associations between diabetes and dementia but really does not shed much more light on the causative mechanism,” he said.

The tau may be involved in the causative process or may be just a marker.

“This study does not distinguish that,” he said.