What causes Alzheimer’s disease? That is the billion-dollar question which remains unanswered to this day. A lot of money has been spent trying to find answers to the mystery of dementia. Most experts in the field point to the buildup of proteins like amyloid beta () and tau and the formation of plaques and neurofibrillary tangles. But this approach doesn’t take into account the role of the vascular system in the development of dementia. New research suggests that leaky blood vessels may play an independent and crucial role in cognitive decline and Alzheimer’s disease.

Blood Vessels in the Brain Matter!

Some people may think of blood vessels a bit like a straw or a garden hose. That is, one continuous hollow tube. In reality a blood vessel is made up of microscopic cells that are firmly attached together. If those attachments become degraded or permeable because of age, infection or inflammation they may begin to leak. Researchers at the University of Southern California believe that blood vessel leakage could a key marker that may show up much earlier in the development of dementia than things like tau and amyloid beta (Nature Medicine, online, January 14, 2019).

One hundred sixty-one people over 45 years old took part in the five-year study. All of them completed cognitive tests that resulted in a score from 0 (normal) to 3 (severe dementia). The scientists also analyzed cerebrospinal fluid for markers of brain capillary permeability. In addition, the volunteers submitted to contrast-enhanced MRIs.

The researchers report a strong correlation between breakdown of the blood brain barrier (BBB) and poor performance on the cognitive tests. Here, in their own words, is their conclusion:

“Our data show that individuals with early cognitive dysfunction develop brain capillary damage and BBB breakdown in the hippocampus irrespective of Alzheimer’s Aβ [amyloid beta] and/or tau biomarker changes, suggesting that BBB breakdown is an early biomarker of human cognitive dysfunction independent of Aβ and tau.”

Translating the Importance of this Research:

We recognize that conclusion is a bit dense to interpret. Keep in mind that billions of dollars have been spent on the amyloid beta (Aβ) and tau theory of dementia. Buildup in the brain of these proteins is believed to cause Alzheimer’s disease.

Drug companies have invested heavily in medications that could lower levels of amyloid in the brain. To date the results have not been promising. The authors of the new research in Nature Medicine report that leaky capillaries can be detected long before Aβ and tau show up.

We interpret that to mean the triggers to dementia may be something the drug companies have not yet considered. The authors conclude:

“Our present findings support that neurovascular dysfunction may represent a previously under appreciated factor contributing to cognitive and functional decline, independent of the classic pathophysiological hallmarks of AD [Alzheimer’s disease].”

In other words, leaky blood vessels could be a big deal and neuroscientists ought to start paying closer attention.

Intestinal Permeability?

Perhaps you have heard of leaky gut. Gastroenterologists have a much classier name: intestinal permeability. When there is damage to the intestinal lining there may be “leakage” of “toxins” into the blood stream. Remember, the lining of blood vessels is made up of cells. The lining of the small and large intestines is also made up of cells firmly attached to each other. Celiac disease, ulcerative colitis (Crohn’s disease, etc) and irritating drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with this syndrome.

Many conventional practitioners have resisted the concept of a leaky gut. If, however, you go to the National Library of Medicine (https://www.ncbi.nlm.nih.gov/pubmed) and search intestinal permeability you will discover thousands of references. Here is just one article published in the highly reputable BMC Gastroenterology (Nov. 18, 2014).

The authors conclude:

“In summary, intestinal permeability, which is a feature of intestinal barrier function, is increasingly recognized as being of relevance for health and disease, and therefore, this topic warrants more attention.”

What Causes Leaky Brain Blood Vessels?

Scientists have known about the blood brain barrier (BBB) for over 100 years. Researchers discovered that if they injected a blue dye into a blood vessel of an animal it would stain the organs of the body, but not the brain. On the other hand, if they injected the blue dye into spinal fluid it would stain the brain but not the rest of the body.

Thus the concept of the BBB was born. In other words, some chemicals could not penetrate from the blood stream into the brain and vice versa. This so-called barrier was thought to protect the brain from toxins and other assaults (Frontiers in Neuroscience, Dec. 16, 2014).

It is, of course, far more complicated than that. We won’t bore you with why some compounds get into the brain and others do not. Suffice it to say, the most obvious question arising from this new research is: what causes leaky brain blood vessels or neurovascular permeability? The answer is also complicated. Brain inflammation can do it. So can the resulting tissue trauma after head injury (Comprehensive Physiology, July 1, 2015). Toxins and brain infections may also disrupt the blood brain barrier and lead to leaky blood vessels.

The Infectious Theory of Alzheimer’s Disease

We are about to tread on thin ice, but the science is accumulating that brain infections may be a significant contributor to dementia. We are talking about herpes virus infections. These are the viruses that cause cold sores and other infections. If you think that sounds too crazy, here are two links to articles that provide scientific evidence to support this hypothesis.

New Research Confirms Link | Herpes Virus Infections and Alzheimer Disease

Can Antiviral Herpes Drugs Reduce the Risk of Alzheimer Disease?

If you would like to dig a bit deeper into this fascinating topic, why not listen to a radio interview we did with Dr. Robert D. Moir. He is Assistant Professor in Neurology at Harvard Medical School. He is also Assistant Professor in Neurology at MGH Neurology Research. His research focuses on the biochemical and cellular mechanisms involved in neurodegeneration in Alzheimer’s disease and aging. His most recent publication is on herpes virus and amyloid beta (Aβ) in Neuron, July 11, 2018.

During this interview you will learn about the brain microbiome. Yes, there are bacteria, viruses and fungi living in our brains. You will also learn about the powerful antibacterial activity of amyloid beta. The FREE one-hour interview can be downloaded at this link. You can also listen to the streaming audio by clicking on the green arrow above the photo of Dr. Moir.

Whether it is possible to reverse capillary permeability and delay or prevent the onset of dementia remains to be seen. We think this new research is incredibly exciting. If the entrenched theories of dementia can be revised, neuroscientists might discover some new approaches to overcome these devastating brain diseases.

Nature Medicine, Jan. 14, 2019

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