Methylene Blue and Alzheimer's Disease Research

As of now, there are nearly 50 million people living with dementia with a prediction of 75 million by 2030. There is an enormous need for new disease-modifying therapies to tackle Alzheimer’s Disease (AD).

Most current therapeutic approaches focus on management of behavioral symptoms or attempting to slow the progress of the disease, but none of these solutions modify the unavoidable course of the disease.

Many people have family members with AD and wonder why there haven’t been any solutions that actually improve behavior or truly preserve the memory loss of their loved ones. They also wonder if this will be their future also. How can they prevent, slow, or reverse the disease? It’s a devastating disease to witness, and often, people are looking for additional things to slow the progress of the disease.

There are problems with current AD research.

According to Professor Dr. Francisco Gonzalez-Lima, who currently works at the Departments of Psychology, Psychiatry, and Pharmacology/Toxicology, and Institute for Neuroscience at the University of Texas at Austin.

Amyloid deposits became popular as the hypothetical cause of AD. Many companies have spent millions of dollars researching amyloid deposits and developing drug therapies that have mostly targeted amyloid beta (Aβ) and tau tangles.

A brain with Alzheimer’s disease contains two types of abnormal structures: extracellular amyloid plaques and intraneural neurofibrillary tangles. The building blocks are amyloid-β (Aβ) peptides for plaques and tau for tangles. The behavioral symptoms in a patient with AD correlate with the increasing level of plaques and tangles. Learn more >>

These are not the best targets for drug therapies for late-onset Alzheimer’s disease, according to one of the world’s leading neuroscientists, Dr. Francisco Gonzalez-Lima, Ph.D.

The issue with amyloid and tau neurofibrillary tangles is that they are consequences of AD and neurodegenerative changes, not causes.

They are what you see after years of the degeneration process already happening in the brain. Aβ and tau will show up in all seniors eventually, and the damage to the brain is already done by the time it appears. One can try to clean up all the deposits, but it will have no relevance for any symptoms of AD. It makes no difference in the outcomes; the drug efforts have been wasted. Why? Because there is no relationship of the current drug therapies with cytochrome oxidase inhibition; Aβ and tau are pathological signs of having a disease.

Drug Therapies for Early-Onset vs Late-Onset AD

There are two different types of AD, although patients with either type will eventually exhibit the same types of symptoms such as behavioral changes, confusion, memory loss, and difficulty making decisions.

Early-onset AD is rare, and only up to 5% diagnosed have this type. This occurs in people younger than 65 years. Late-onset AD happens in people over 65 years of age and is the most common form.

“Clinical trials focusing on drugs that modify β-amyloid (Aβ) have not improved the outcome of Alzheimer’s disease (AD). Elevated biomarkers of Aβ and tau may be better for predicting early dementia status, rather than the more common typical later dementia status that is seen in most patients.”

– Taken from β-Amyloid and tau drive early Alzheimer’s disease decline while glucose hypometabolism drives late decline (Hammond et al., 2020)

As our bodies age, we have chronic weakening in our circulatory system. This decreases the blood flow (therefore, oxygen supply) to the brain. Crucial to this process is cytochrome oxidase (CO), which is a mitochondrial enzyme that catalyzes a cell reaction vital to aerobic energy production.

Since 95% of the population has late-onset AD, research should be about mitochondrial dysfunction and CO; it is the inability of the brain to use oxygen to prevent oxidative damage.

Dr. Gonzalez-Lima often discusses his research with “fresh brains”.

The Host of the Decoding Superhuman podcast, Boomer Anderson, asked Dr. Gonzalez-Lima if Cytochrome Oxidase (CO) is related to longevity. Dr. Gonzalez-Lima thinks the answer is yes. If you can upregulate CO, you can increase lifespan.

The primary deficiency in patients with AD was a downregulation of CO. This is how Dr. Gonzalez-Lima got interested in studying methylene blue.

Research on Methylene Blue and Its Effects on AD

Methylene blue has shown to be beneficial in animals and limited human studies on mitochondrial function.

*There is a FDA warning for potential drug interaction between methylene blue and serotonergic psychiatric medications. More Information >>

Podcast Interviews with Dr. Francisco Gonzalez-Lima

Drive with Dr. Peter Attia: #38
Francisco Gonzalez-Lima, Ph.D.: Advancing Alzheimer’s disease treatment and prevention — Is AD actually a vascular and metabolic disease?

STEM-Talk: Episode 107
Francisco Gonzalez-Lima discusses methylene blue and near-infrared light as therapies for cognitive disorders.

Decoding Superhuman Podcast
Methylene Blue with Dr. Francisco Gonzalez-Lima and host Boomer Anderson.

Methylene blue modulates functional connectivity in the human brain
Methylene blue USP (MB) is a FDA-grandfathered drug... Read on >>

Multimodal Randomized Functional MR Imaging of the Effects of Methylene Blue in the Human Brain
To investigate the sustained-attention and memory-enhancing neural correlates... Read on >>

Protection against neurodegeneration with low-dose methylene blue and near-infrared light
Targeting mitochondrial respiration may be beneficial... Read on >>

Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue
This paper provides the first review of the memory-enhancing and neuroprotective metabolic mechanisms... Read on >>