Amyloid Protein-Lowering Drugs vs Decreasing Homocysteine

Worldwide 46.8 million people have dementia and in the UK, 1 in 14 people over 65 have Alzheimer’s, the most prevalent form of dementia; and increasingly dementia sufferers are also struggling with other chronic conditions, such as diabetes and depression. Research on new strategies for earlier diagnosis is among the most active areas in Alzheimer’s science, as the majority of cases are diagnosed when irreversible brain damage or mental decline has already occurred. 

The amyloid protein test used for earlier diagnosis

new study released in August 2019 found that a blood test to measure amyloid beta, a protein found in the brain that is involved in the pathophysiology of Alzheimer’s and cognitive decline, is 94% accurate in identifying the developments of Alzheimer’s disease earlier, when in combination with age and genetics (testing positive for the APOE4 gene) as risk factors. Whilst this is a positive development for future considerations in treating Alzheimer’s, there has been no successful amyloid-lowering drug trial to date. In addition, it is well-known that the damaging clumps of amyloid protein can begin to develop and lead to brain atrophy decades before an individual even begins to experience symptoms of memory loss and cognitive function, so unless testing is given earlier on in life as a preventative measure, an amyloid-lowering drug when the damage has already been caused may not be very effective. 

To date, the majority of research into the treatment of Alzheimer’s has been focused on the “amyloid hypothesis”. In 2018 alone, the US National Institutes of Health spent $1.9 billion on Alzheimer’s research. However, according to a study carried out last year, there has been a 99% failure rate in the development of drugs that target this disease. Questions about the reliability of the amyloid protein hypothesis are being posed by scientists, after various studies discovering how amyloid plaques actually function as a type of sticky defence against bacterial invasion, lead to a different hypothesis. In one significant study, where mice that were genetically engineered to make Alzheimer’s proteins had bacteria injected into their brains, researchers found that amyloid plaques engulfed bacterial cells overnight, suggesting a protective mechanism.  

Why we cannot ignore the link between high homocysteine levels and Alzheimer’s 

According to a Consensus Statement released by an international panel of experts on dementia, research has shown, time and time again, that having high homocysteine (Hcy) levels, and low folic acid and B12 levels in the blood correlate with an increased risk for Alzheimer’s disease. An earlier review written by Professor David Smith in 2008, highlighted that there are a total of ‘seventy-seven cross-sectional studies on more than 34,000 subjects and 33 prospective studies on more than 12,000 subjects’…that…‘have shown associations between cognitive deficit or dementia and homocysteine and/or B vitamins.’ In a meta-analysis published in 2014 by BMC Public Health, raised homocysteine was considered to be one of the three strongest risk factors, along with low education and decreased physical activity. In addition, two further trials have clearly shown that lowering homocysteine, through the supplementation of B vitamins, reduced age-related cognitive decline in normal ageing and also slowed down both brain atrophy and cognitive decline in people with Mild Cognitive Impairment. In one of the studies, 270 people over 70 with Mild Cognitive Impairment were recruited to trial the efficacy of B vitamins to prevent the progression of Alzheimer’s. MRI scans were done at recruitment and half the participants were given high doses of three B vitamins (B6, B9 and B12), half took a placebo tablet. After 2 years, participants were scanned again and scientists found that the rate of brain atrophy in those treated with the B vitamins was on average 30% slower than those taking placebo. In addition, in those that had the highest homocysteine levels at baseline, the effect of B vitamin treatment was even more potent, helping to slow down brain atrophy by 53%. This result fits all the criteria for a disease-modifying treatmentand so is especially important. There is, therefore, ample evidence to propose that lowering homocysteine by giving appropriate supplemental levels of homocysteine lowering nutrients, including B6, B12 and folic acid, would reduce risk. However, last year, in a commission published by the Lancet, 9 modifiable risk factors were outlined, clearly excluding homocysteine:  

Mid-life hearing loss – responsible for 9% of the risk Failing to complete secondary education – 8% Smoking – 5% Failing to seek early treatment for depression – 4% Physical inactivity – 3% Social isolation – 2% High blood pressure – 2%Obesity – 1% Type 2 diabetes – 1% 

Ignoring homocysteine is surprising, since a meta-analysis from the National Institute of Aging estimated that about 22% of Alzheimer’s disease may be caused by raised levels of homocysteine. It’s about time health authorities like the NHS took into account the evidence concerning the significance of homocysteine in the pathogenesis of Alzheimer’s. Integrating homocysteine testing and inexpensive B vitamin-based treatment into the heart of mainstream health strategies on Alzheimer’s could potentially play a vital role in the prevention of dementia, if caught early enough. Every 3 seconds, someone in the world develops dementia and the International Alzheimer’s Society estimates that by 2050 there will be 131.5 million people living with this disease. This is not something we can ignore.