Bone loss linked to Alzheimer's disease

 

Alzheimer's disease remains one of the top neurodegenerative disorder affecting people worldwide. As part of research to provide early treatment for this brain disorder, a mouse model has been used to study its link with early bone degeneration.

Researchers from the Northeast Ohio Medical University said that their findings are important to create a detection biomarker because bone loss occurs in the early onset of the disease. This means that early diagnosis can be conducted even without brain examination.

According to the study, patients suffering from the brain disorder commonly manifest reduced bone mineral density. Osteoporosis often takes place before dementia begins. Despite these correlations, the mechanisms behind this link remain unanswered. With this, the researchers hypothesize that bone degeneration is a result of lack of serotonin production. This brain chemical is responsible for sleep and mood and is believed to be affected by Alzheimer's.

The researchers used "htau mice," which were genetically modified to have human-type tau protein in their brains. Their bone mineral density was measured before the manifestation of excessive tau production. The results showed that there was a significant loss in bone density especially in males compared to healthy mice. Further, changes in the dorsal raphe nucleus (DRN) which is a "pivotal structure in the regulation of the adult skeleton" and production of serotonin were observed.

The study concluded that bone density loss happens before brain degeneration. The scientists also revealed that changes in tau protein occur in the brainstem where serotonin-producing cells exist.

Lead researcher Christine Dengler-Crish said that "measurement of bone density, which is routinely performed in the clinic, could serve as a useful biomarker for assessing AD risk in our aging population." She added that studying the serotonin system may help in the development of potential therapies for AD.

In a separate study by the Saitama Medical University in Japan, a drug called Donepezil was found to be effective in preventing bone loss and treating Alzheimer's. Dr. Tsuyoshi said that the drug could correct bone mass while improving cognitive function. He added that "from the viewpoint of medical economics, this dual purpose could reduce the cost of treating these diseases."

Alzheimer's is the most common culprit of dementia among seniors. It is the sixth deadliest disease in the United States. People suffering from this disease lose their memories and ability to reason, think, and decide. Once the disease progresses, patients also forget to take care of themselves. Existing research only shows that the excessive accumulation of beta-amyloid and tau proteins in the brain is a hallmark of the disease. This accumulation clogs up the neurons and causes their death.

Causes of Alzheimer's disease 

Alzheimer's disease is caused by parts of the brain shrinking (atrophy), which affects the structure and function of particular brain areas.
It's not known exactly what causes this process to begin. However, in the brains of people with Alzheimer's disease, scientists have found amyloid plaques (abnormal deposits of protein), neurofibrillary tangles (containing tau) and imbalances in a chemical called acetylcholine.
It's also common to have a degree of vascular damage in the brain.
These reduce the effectiveness of healthy neurons (nerve cells that carry messages to and from the brain), gradually destroying them.
Over time, this damage spreads to several areas of the brain. The first areas affected are responsible for memories.

Increased risk

Although it's still unknown what triggers Alzheimer's disease, several factors are known to increase your risk of developing the condition.

Age

Age is the single most significant factor in the development of Alzheimer's disease. The likelihood of developing the condition doubles every five years after you reach 65 years of age.
However, it's not just older people who are at risk of developing Alzheimer's disease. Around 1 in 20 people with the condition are under 65. This is called early onset Alzheimer's disease and it can affect people from around the age of 40.

Family history

The genes you inherit from your parents can contribute to your risk of developing Alzheimer's disease, although the actual increase in risk is small if you have a close family member with the condition.
However, in a few families, Alzheimer's disease is caused by the inheritance of a single gene, and the risks of the condition being passed on are much higher.
If several of your family members have developed dementia over the generations, it may be appropriate to seek genetic counselling for information and advice about your chances of developing Alzheimer's disease when you are older.
The Alzheimer's Society website has more information about the genetics of dementia.

Down's syndrome

People with Down's syndrome are at a higher risk of developing Alzheimer's disease.
This is because the genetic fault that causes Down's syndrome can also cause amyloid plaques to build up in the brain over time, which can lead to Alzheimer's disease in some people.

Head injuries

People who have had a severe head injury have been found to be at higher risk of developing Alzheimer's disease.

Cardiovascular disease

Research shows that several lifestyle factors and conditions associated with cardiovascular disease can increase the risk of Alzheimer's disease.
These include:

• smoking
• obesity 
• diabetes 
• high blood pressure
• high cholesterol

You can help reduce your risk by:

• stopping smoking
• eating a healthy, balanced diet
• leading an active life, both physically and mentally
• losing weight if you need to
• drinking less alcohol
• having regular health checks as you get older
  Fewer than 5 percent of cases of Alzheimer's disease have a clear genetic cause, making it hard to predict who will develop the devastating brain-wasting disorder. There is an urgent need to develop biomarkers and early treatments before the symptoms of decline take hold and destroy lives. Now, using a mouse model of Alzheimer's disease, researchers discover a link between early bone loss and brain degeneration that may begin to address this need.
  
  Years before the symptoms emerge, abnormal protein deposits are already forming throughout the brain in people with Alzheimer's disease.
  The researchers - from Northeast Ohio Medical University (NEOMED) in Rootstown - report their findings in the Journal of Alzheimer's Disease.
  Their study is important because it identifies alterations that appear to occur in the very early stages of Alzheimer's disease, and because they affect bone, may offer a biomarker for earlier detection that does not involve examining the brain.
  Among older adults, Alzheimer's disease is the most common cause of dementia, a progressive brain disorder that gradually robs people of their ability to remember, think, reason, and make decisions. Eventually, the symptoms become so severe that patients can no longer take care of themselves.
  Alzheimer's disease is ranked as the sixth leading cause of death in the United States, where estimates suggest there are more than 5 million people living with the disease.
  Among older Americans, the disease is thought to be the third leading cause of death, just behind heart disease and cancer.
  

  Need for biomarkers of early disease

  Scientists are still trying to understand the complex, incurable - and seemingly unstoppable - changes that take place in the brain of people with Alzheimer's disease.
  However, they do know that years before the symptoms emerge, abnormal deposits of beta-amyloid and tau proteins are forming throughout the brain, gradually clogging up brain cells so they stop working and die.
  There is an urgent need to find ways to identify and stop these early brain changes before they damage the brain
  Reduced bone mineral density and the disease it leads to - osteoporosis - are much more common in people with Alzheimer's disease. The bone conditions often emerge before the dementia symptoms are spotted. However, the underlying mechanisms linking them are unclear.
  The researchers behind the new study had a hunch that bone loss is an additional early symptom of Alzheimer's disease itself, due to a dysfunction in the production of serotonin, a brain chemical that controls mood and sleep - two processes that are also affected early in Alzheimer's disease.
  So they set out to investigate, using "htau mice" - mice genetically engineered to have human forms of a type of tau protein that becomes faulty in Alzheimer's disease and disrupts an important internal cell structure called microtubules.
  

  Bone loss in htau mice linked to serotonin deficits

  The researchers measured bone mineral density in the htau mice before they developed significant signs of tau abnormality. They found significantly reduced bone mineral density compared with normal mice - especially in the males.
  Further examination of the htau mice revealed major cell changes in a region of the brainstem known as the dorsal raphe nucleus (DRN) - "a pivotal structure in the regulation of the adult skeleton," note the authors. The DRN also produces most of the brain's serotonin.
  The researchers also found higher levels of abnormal tau protein in the same area of the brain as early as 4 months of age in the htau mice.
  They conclude that their findings show reduced bone mineral density occurs earlier than the overt brain degeneration seen in a tau-based mouse model of Alzheimer's disease and that alterations in tau protein occur in the serotonin-producing cells of the brainstem of such mice.
  The team suggests further studies should now look for the molecular mechanism that links bone loss to reduction in serotonin in early Alzheimer's disease in humans.
  Should that be found, then as lead author Christine Dengler-Crish, assistant professor of pharmaceutical sciences, and anatomy and neurobiology at NEOMED, suggests:
  "Measurement of bone density, which is routinely performed in the clinic, could serve as a useful biomarker for assessing AD [Alzheimer's disease] risk in our aging population."
  

  "The findings of this study motivate us to explore the serotonin system as a potential new therapeutic target for this devastating disease."
  

  Prof. Christine Dengler-Crish