High cholesterol, glucose and gum disease linked to Alzheimer’s

Published: Aug 19, 2022

By Mark Terry

BioSpace

Researchers studying Alzheimer’s disease have published new studies supporting links between Alzheimer’s and other diseases, as well as potential risk factors for developing the disease later in life.

Although the accumulation of two abnormal proteins in the brain, beta-amyloid and tau, are two of the primary culprits for Alzheimer’s disease,  other factors linked to that accumulation are still being determined.

Here is a look at the latest Alzheimer’s research, includes studies surrounding insulin resistance in brain cells, role of dysfunctional immune cells and neuroinflammation caused by infections and other factors. 

Cholesterol and Blood Sugar Levels May Increase Risk of Alzheimer’s

New findings from the Boston University School of Medicine suggest that high cholesterol and glucose levels in people as young as 35 years old may increase the risk of Alzheimer’s later in life. The research was published in the scientific journal Alzheimer’s & Dementia.

Alzheimer’s disease has often been referred to as Type 3 diabetes. Being overweight and living with Type 2 diabetes increases the risk of developing Alzheimer’s. Overall, all the risk factors for cardiovascular (CV) disease, including obesity, diabetes and high cholesterol, are also known risk factors for Alzheimer’s.

Many studies have been conducted in people 55 years and older, but this new study evaluated CV risk factors in people 35 to 50, 51 to 60 and 61 to 70. The researchers also pulled data from the Framingham Heart Study, a multigenerational CV study.

The researchers looked at a set of participants who started the study in the early 1970s and were evaluated every four years. There were 4,932 participants between 5 and 70 years of age at their first exam, with an average age of 36. At each check-in, their glucose, cholesterol, and triglycerides levels were checked, as well as blood pressure, body mass index and smoking status. Later, cognitive tests were included.

High-density lipoproteins (HDL, aka, the good cholesterol) and higher triglyceride levels in early adulthood and increased blood sugar levels in middle adulthood increased the risk of Alzheimer’s. The authors noted, “The effects of these risk factors, particularly glucose level, may not be AD specific and may contribute to incidence of other forms of dementia.”

Type 3 diabetes would more narrowly be defined as when brain cells can’t respond to insulin, which would result in loss of memory and cognition. One of the best-known gene abnormalities associated with Alzheimer’s disease, APOE4, is involved in how the brain processes insulin.

The APOE gene codes for a protein called apolipoprotein E, which combines fats in the body to form lipoproteins, which are responsible for packaging cholesterol and other fats and carrying them through the blood. So, it would make sense that some form of cholesterol and blood sugar dysfunction is a factor in Alzheimer’s disease.

APOE, Alzheimer’s and Glaucoma

Researchers at Mass. Eye and Ear, Brigham and Women’s Hospital and Mass/ General Brigham published research linking the APOE gene commonly associated with Alzheimer’s to protection against the eye disease glaucoma.

APOE4 blocks a disease cascade that causes the destruction of retinal ganglion cells in glaucoma. In a mouse model, researchers were able to prevent the destruction of neurons in the eyes of mice with glaucoma by using a drug that targeted the APOE signaling pathway. In a separate mouse model, using a drug called Galectin-3, which is regulated by the APOE gene, they prevented the death of retinal ganglion cells, which cause blindness in glaucoma.

“Our research provides greater understanding of the genetic pathway that leads to irreversible blindness in glaucoma, and importantly, points to a possible treatment to address the root cause of the vision loss,” Dr. Milica Margeta, M.D., Ph.D., lead author and a glaucoma specialist and scientist at Mass Eye and Ear and assistant professor of ophthalmology at Harvard Medical School, said. “This study shows that the APOE-mediated disease cascade is clearly harmful in glaucoma, and that when you interfere with it genetically or pharmacologically, you can actually stop the disease.”

New Research Supports Link Between Gum Disease and Alzheimer’s

Another study has been published supporting a theorized link between gum disease and Alzheimer’s progression.

The study, published in Frontiers in Aging Neuroscience, showed researchers at Tufts University School of Dental Medicine found a connection between the bacteria Fusobacterium nucleatum (F. nucleatum), often found in periodontal disease, and Alzheimer’s.This is not a particularly new finding, although the association with this species of bacteria is new.

“In this study, our lab is the first to find that Fusobacterium nucleatum can generate systemic inflammation and even infiltrate nervous system tissues and exacerbate the signs and symptoms of Alzheimer’s disease,” said Jake Jinkun Chen, DMD, MDS, PhD, professor of periodontology and director of the Division of Oral Biology at Tufts.

Interestingly, F. nucleatum can cause severe generalized inflammation, a common symptom of many chronic illnesses, including Type 2 diabetes and Alzheimer’s disease. Their study in mice found that F. nucleatum infection caused an abnormal proliferation of microglial cells, which are immune cells found in the brain.

Dysfunctional microglial cells have also been associated with Alzheimer’s disease. The extra microglial cells appeared to create an increased inflammatory response.

Source: BioSpace