Cell Death

Periodontitis raises dementia risk

A 10-year South Korean study using data from 262,349 older adults (50+) has found that those with chronic periodontitis had a 6% higher risk for dementia than did people without periodontitis. This connection was true despite behaviors such as smoking, consuming alcohol, and remaining physically active.


Gum disease link to Alzheimer's explained

Gum disease has been linked to Alzheimer's as a risk factor, and now an animal study provides evidence that Porphyromonas gingivalis (Pg), the bacterium associated with chronic gum disease, colonizes the brain and increases production of amyloid beta.

Moreover, the bacterium's toxic enzymes (gingipains) have been found in the neurons of patients with Alzheimer’s. Gingipain levels were associated with two markers: tau, and ubiquitin (a protein tag that marks damaged proteins).

When molecule therapies targeting Pg gingipains were applied, there was reduced bacterial load of an established Pg brain infection, blocked amyloid-beta production, reduced neuroinflammation and protected neurons in the hippocampus.

Around half the population are said to have this bacteria in some form, and around 10% of those with the bacteria will develop serious gum disease, loose teeth, and have an increased risk of developing Alzheimer´s disease.



Mouse study links periodontal disease bacteria to greater amyloid plaques, brain inflammation, neuron death

A mouse study found that long-term exposure to periodontal disease bacteria resulted in significantly higher amounts of amyloid beta plaque, more brain inflammation and fewer intact neurons. It’s important to note that the mice used in the study were not genetically engineered to develop Alzheimer's.


A fruitfly study suggests that losing neurons is not necessarily a bad thing. The study used fruitflies genetically engineered to express human amyloid-beta proteins in their brains. When neuronal death was blocked, the flies developed even worse memory problems, worse motor coordination problems, died earlier and their brain degenerated faster. However, when the normal process of cell competition was enhanced, the flies showed an impressive recovery.

Cell competition is a cell quality control mechanism, by which fitter cells trigger the suicide of less fit ones. Research has shown that cell competition is a normal, powerful anti-aging mechanism.

The findings suggest that neuron loss reflects the brain protecting itself from defective neurons, not something that should be prevented. (What we want, of course, is for the neurons not to be damaged.)


New research supports the classification system for preclinical Alzheimer’s proposed two years ago. The classification system divides preclinical Alzheimer's into three stages:

Stage 1: Levels of amyloid beta begin to decrease in the spinal fluid. This indicates that the substance is beginning to form plaques in the brain.

Stage 2: Levels of tau protein start to increase in the spinal fluid, indicating that brain cells are beginning to die. Amyloid beta levels are still abnormal and may continue to fall.


Long-term evaluation of 311 cognitively healthy older adults (65+) found 31% with preclinical Alzheimer’s, of whom 15% were at stage 1, 12% at stage 2, and 4% at stage 3. This is consistent with autopsy studies, which have shown that around 30% of cognitively normal older adults die with some preclinical Alzheimer's pathology in their brain. Additionally, 23% were diagnosed with suspected non-Alzheimer pathophysiology (SNAP), 41% as cognitively normal, and 5% as unclassified.

Five years later, 2% of the cognitively normal, 5% of those with SNAP, 11% of the stage 1 group, 26% of the stage 2 group, and 56% of the stage 3 group had been diagnosed with symptomatic Alzheimer's.



A five-year study involving 525 older adults (70+) found 46 had Alzheimer’s or aMCI and a further 28 went on to develop the conditions. The blood levels of 10 specific lipids predicted with more than 90% accuracy whether an individual would go on to develop either Alzheimer’s or aMCI within 2-3 years. The researchers speculate that the lower lipid levels could be an early indication that brain cells are beginning to lose their integrity and break down.

The continual failures in human clinical trials of promising therapies has led to a growing belief that once the cognitive symptoms of the Alzheimer’s have emerged, it may be too late to slow or reverse the neurological damage. However, treatments begun early enough may be more effective. This is why early diagnosis of Alzheimer’s risk is so critical.




[3588] Mapstone, M., Cheema A. K., Fiandaca M. S., Zhong X., Mhyre T. R., MacArthur L. H., et al.
(2014).  Plasma phospholipids identify antecedent memory impairment in older adults.
Nature Medicine. 20(4), 415 - 418.


Study links Alzheimer's disease to abnormal cell division

Neurons affected by Alzheimer’s and many other neurodegenerative diseases often start to divide before they die. A new mouse study shows that this abnormal cell division starts long before amyloid plaques or other markers of the disease appear, suggesting a new approach to therapy for Alzheimer's. The findings also shed new light on the theory that the accumulation of amyloid beta in the brain causes the neuron death in Alzheimer’s, indicating that micro-molecular aggregates (tiny clumps made up of several amyloid beta molecules) rather than amyloid plaques may trigger the disease.

Yang, Y., Varvel, N.H., Lamb, B.T. & Herrup, K. 2006. Ectopic cell cycle events link human Alzheimer's disease and APP transgenic mouse models. The Journal of Neuroscience, 26 (3), 775-784.


Abnormal cell division possible precursor of Alzheimer's

A study of genetically engineered mice sheds more light on the causes of Alzheimer’s. The study looked at what the reasons for neuron death apart from neurofibrillary tangles; they found an abnormal type of cell division occurring in tau proteins that may activate a cascade of abnormal events.

Andorfer, C., Acker, C.M., Kress, Y., Hof, P.R., Duff, K. & Davies, P. 2005. Cell-Cycle Reentry and Cell Death in Transgenic Mice Expressing Nonmutant Human Tau Isoforms. Journal of Neuroscience, 25, 5446-5454.


Nerve cell death in Alzheimer's is caused by a failed attempt at cell division

Researchers have uncovered a key piece of missing evidence in the proof that nerve cell death in Alzheimer's disease is caused by a failed attempt at cell division. They have found a significant number of brain cells in Alzheimer's patients with extra copies of chromosomes, showing attempts at cell division in cells that are not supposed to divide. This effort to divide may be the cause of the nerve degeneration and dementia in Alzheimer's disease. "It's almost as if Alzheimer's disease were a novel form of cancer." Cancer is characterized by uncontrolled cell division. In this study, scientists found uncontrolled cell division, arrested in the midst of the process, is the likely cause of the nerve cell destruction. It is speculated that the plaques which are a hallmark of Alzheimer's disease brain cells trigger an inflammatory response in the brain, and that this response brings with it proteins that trigger cell division. This finding may signal a new approach to the treatment of Alzheimer's, trying to prevent signals for the inflammatory response from reaching the cells or to prevent the cells from responding to the signals to divide.

Yang, Y., Geldmacher, D. S., & Herrup, K. (2001). DNA Replication Precedes Neuronal Cell Death in Alzheimer’s Disease. The Journal of Neuroscience, 21(8), 2661–2668. Retrieved from http://www.jneurosci.org/content/21/8/2661


Overproduction of the brain chemical galanin might contribute to cognitive decline

Overproduction of the brain chemical galanin during the early stages of Alzheimer’s may have an negative effect on the brain and contribute to the cognitive decline of patients, according to a study involving transgenic (mutated) mice. The study suggests the overproduction of galanin might be a response to the deterioration of brain cells ( people with Alzheimer's have twice as much galanin in certain areas of the brain as peers who die of something else). While initially galanin might be beneficial, as the disease progresses, the overexpression of galanin may become its own problem, contributing to cognitive decline. It seems that the memory loss that occurs with Alzheimer's may be caused by the combination of cell death and excess galanin. It may be that a drug that blocks galanin would slow or reverse the mental damage caused by the disease.

Steiner, R. A., Hohmann, J. G., Holmes, A., Wrenn, C. C., Cadd, G., Juréus, A., … Crawley, J. N. (2001). Galanin transgenic mice display cognitive and neurochemical deficits characteristic of Alzheimer’s disease. Proceedings of the National Academy of Sciences, 98(7), 4184–4189. doi:10.1073/pnas.061445598 .