Two molecules explain Alzheimer’s ‘mystery’ and enable early detection

Of the 6.2 million Americans over the age of 65 with Alzheimer’s disease, almost two-thirds are women, meaning Alzheimer’s is almost twice as common in women as in men.

While the exact reason why has been a mystery, there are a couple of theories…

Women tend to live longer than men, and the most significant risk factor for Alzheimer’s is age. It skyrockets in those aged 75 and older.

Also, women are twice as likely as men to have an autoimmune disease. Since some experts say beta-amyloid is a normally occurring molecule that is part of the brain’s immune system, an overactive immune system seems a logical connection.

Changes in hormones have also linked Alzheimer’s to women, not only the loss of estrogen, but higher levels of cortisol in midlife as well.

Fortunately, recent research may not only explain why women are at higher risk of the disease — but also lead to the development of a simple blood test that could detect Alzheimer’s in the early stages…

The roles of acetyl-L-carnitine and free carnitine

An international team of researchers measured blood levels of two amino acids essential for healthy brain function — acetyl-L-carnitine and free carnitine — in two separate groups of men and women in Brazil and California. Some were diagnosed with varying degrees of cognitive impairment, while others were cognitively healthy.

The researchers discovered that blood levels of acetyl-L-carnitine were lower in both women and men with mild cognitive impairment and Alzheimer’s disease. In addition, levels of free carnitine, a byproduct of acetyl-L-carnitine in reactions essential to brain function, showed a steady decline in women in amounts related to the severity of their cognitive decline.

Tests also indicated that levels of the two molecules aligned in direct proportion to increased levels of amyloid beta and tangled tau protein, both of which are long considered markers of Alzheimer’s severity.

The research team’s accuracy in diagnosing Alzheimer’s severity rose from more than 80% when using either the two blood molecules or amyloid beta and tangled tau protein levels from cerebrospinal fluid, to 93% when using both.

The fact that declines in men were only evident in acetyl-L-carnitine reveals a disease-specific difference between the sexes and could explain the higher risk of Alzheimer’s in women.

“Our findings offer the strongest evidence to date that decreased blood levels of acetyl-L-carnitine and free carnitine could act as blood biomarkers for identifying those who have Alzheimer’s disease, and potentially those who are at greater risk of developing early dementia,” says study lead investigator Dr. Betty Bigio, a professor at NYU Grossman School of Medicine.

“Because declines in acetyl-L-carnitine and free carnitine tracked closely with the severity of Alzheimer’s disease, the molecular pathways involved in their production offer other possible therapeutic targets for getting at the root cause of the disease and potentially intervening before permanent brain damage occurs,” said senior study investigator Carla Nasca, PhD. Nasca is an assistant professor in the Departments of Psychiatry and Neuroscience at NYU Grossman School of Medicine.

Dr. Nasca suggests that further research is needed to clarify the role of acetyl-L-carnitine in brain chemistry. If further studies confirm the latest findings, she adds, they could be used to develop a simple blood test for dementia and to track the progression of Alzheimer’s.

Getting enough acetyl-L-carnitine

Previous studies have found that acetyl-L-carnitine can help improve Alzheimer’s symptoms by enhancing cognitive function and mitigating cognitive impairment.

One study found memory and cognitive scores in Alzheimer’s patients given 2,250 to 3,000 mg daily of acetyl-L-carnitine improved 2.8 times better than placebo-treated subjects over 12 weeks.

Carnitine is produced naturally by the body through synthesis by the liver and kidneys. However, levels of carnitine in the body do decline with age, with one study finding levels were about 20% lower in aged rats.

So if you’re older, it may be a good idea to consume foods rich in carnitine. These include animal products such as red meat, poultry, fish and dairy products. Fruits, vegetables and grains contain negligible amounts of the amino acid.

You could also try acetyl-L-carnitine supplements. Just be careful if you’re taking blood thinners or drugs for lowering blood sugar — you’ll want to talk to your doctor first before adding acetyl-L-carnitine to the mix.

Sources:

Study advances possible blood test for early-stage Alzheimer’s disease — EurekAlert!

Sex differences in mitochondrial free-carnitine levels in subjects at-risk and with Alzheimer’s disease in two independent study cohorts — Molecular Psychiatry

Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update — Nutrients

Why are women more likely to develop Alzheimer’s disease? — Harvard Health Publishing

Acetyl-L-carnitine supplementation restores decreased tissue carnitine levels and impaired lipid metabolism in aged rats — Journal of Lipid Research

Carnitine — National Institutes of Health