Brain Plaques, Tangles & Alzheimer's

The Promise of a Precious Ecosystem - the Amazon Rainforest?

With the aging demographics there is major concern about the societal burden of cognitive decline as well as the emotional impact of Alzheimer's Disease. Families of the afflicted, including my own, find the disease(s) to be particularly cruel and draining. Diagnostically we define these diseases by their impact on memory, behavior & performance as well as anatomical changes such as brain plaques (beta-amyloid fibrils) and tangles (tau protein filaments & aggregates). 

The research goal is to define an approach that either prevents these events and ideally reverses them if they are established, or both. Recent research has offered several approaches that really require more work but allow us to form concepts and define possible treatments.

Cholesteryl Esters

These are the storage units of cholesterol in cells. Research has shown that by lowering cholesteryl esters the levels of tau and Ab plaques are reduced in AD patients. https://health.ucsd.edu/news/releases/Pages/2019-01-24-untangling-tau-researchers-find-a-druggable-target-for-treating-alzheimers.aspx Included in the rationale is that the brain contains 20% of the cholesterol in the body, although the use of statins to lower cholesterol for this purpose remains very controversial. Recent observations have noticed benefits with a HIV drug through this proposed mechanism.

Manipulating Neurotransmitters

The National Institute of Aging offers a variety of pharmacological approaches in the management of Alzheimer’s but I would characterize this as an approach that is designed to offer short term relief by improving the effectiveness of neurotransmission rather than modifying the underlying cause. https://www.nia.nih.gov/health/how-alzheimers-disease-treated These interventions may be directed at acetylcholine in mild disease, and with NMDA & glutamate in more established presentations. While it may help in the short term setting it is not the breakthrough that they we all seek.

Inflammation, Vascular Damage & Leaky Blood-Brain-Barrier

Moving back to potential causative issues, considerable focus has been on inflammation as a driver, which may occur as a result of or drive vascular damage and a compromised blood brain barrier. These events are aligned with what we know about lifestyle and risk factors as predictors of cognitive decline.

There is a huge research effort devoted to “untangling” the web of interactions that drive the various presentations. The angst resides in a potential failure of these efforts or being unaffordable once they are identified and presented. That is the ROI for the research investment, although investing in the health of a society should be the desired goal of any large R&D effort.

What if?

What if there is a remarkable breakthrough that is affordable and has its origins in nature? What if a breakthrough was a renewable, plant-based resource? What if the science showed that it acted on the precursor inflammatory event, and that it not only worked in a preventative manner, but also showed efficacy in resolving established plaques and tangles?

What if?

Recently there was a substantial research study that demonstrated these characteristics. The natural product extract was able to:

·     Prevented the formation of plaques and tangles in the laboratory setting

·     Reduce the levels of established plaques and tangles in experimental models of AD, and in the laboratory disrupt aggregates of Ab fibrils almost instantly

·     Is associated with improved cognitive performance in afflicted individuals

And the research was published in the prestigious journal “Nature: Scientific Reports” https://www.nature.com/articles/s41598-019-38645-0

The source was of this breakthrough is a vine that grows in the Amazon Rainforest, Cat’s claw (Uncaria tomentosa or Uncaria guianensis). I discovered that this traditional medicine was a remarkable inhibitor of chronic inflammation via suppression of transcriptomic (epigenetic) mechanisms over 20 years ago and proceeded to document it benefits in numerous preclinical and clinical forms of inflammation. https://www.dhirubhai.net/pulse/managing-inflammation-harnessing-power-amazon-mark-js-miller/

The authors of the Nature article discuss how a component of cat’s claw, a catechin dimer, called PTI-777, is able to cross the blood-brain-barrier and enter the brain tissue within two minutes of being in the blood. This is remarkable for a polar compound. This compound, proanthocyanidin B2, is a dimer of two forms of epicatechin, and is a featured constituent of this traditional Amazonian medicine. Traditionally, the bark of the vine cat’s claw is made into a tea (hot water decoction) and is used for various conditions characterized by chronic inflammation. Indeed, it is revered for those applications.

My research has described it as being the most potent inhibitor of NF-kB activation of botanical origin that is known. NF-kB is the master controlling gene expression during inflammation. Suppressing this switch down-regulates the drivers of tissue damage while at the same time activating the repair signals.

The observations that its components can cross the blood-brain-barrier and physically interact with amyloid plaques and tangles (tau) to untangle them, is remarkable. While I am certain the authors of the Nature article are looking to protect the IP around their discovery, the bottom line is that there is value in traditional medicines. When one combines the “old knowledge” with state-of-the-art scientific investigations we may be able to give the masses new hope and the possibilities of am enhanced quality of life that they seek. That is a major reason why we must protect biodiversity and ecosystems that offer us breakthroughs that we only just appreciating.

There is always value in posing the question – What if?

This article is dedicated to my Mother-in-Law, Kate Perkins, whose career was one of immense devotion, innovation and caring for children in the Burns Unit, Women & Children's Hospital, Adelaide, Australia, and whose memories have been stolen by Alzheimer's.