Researchers from NYU Langone Health and colleagues in the United States and Brazil undertook a new study that discovered that lower levels of two naturally occurring compounds in the blood are highly associated with increasing Alzheimer's disease, particularly in women. The study found a significant variation in how the disease progressed between men and women. The findings appeared in the journal Molecular Psychiatry.Alzheimer's disease affects six million Americans, the vast majority of whom are women over the age of 65. Researchers discovered that men and women with mild cognitive impairment and Alzheimer's have decreased levels of the protein acetyl-L-carnitine. However, the amount of free carnitine in women's blood decreased in direct proportion to how much their cognitive function declined. Men's blood levels of acetyl-L-carnitine decreased dramatically, while free carnitine did not, showing a significant gender difference.

One of the study's key findings was that men experienced significant declines in acetyl-L-carnitine but not in free carnitine, indicating a significant gender difference.

More testing revealed that higher quantities of these chemicals in the blood corresponded to higher levels of amyloid beta and tangled tau proteins, two well-known indicators of Alzheimer's disease. Researchers were able to accurately diagnose Alzheimer's 93% of the time when they used all of these tests together. This is up from more than 80% accuracy when they only used amyloid beta and tau levels or blood molecules. 

"Our results show the strongest proof to date that lower levels of acetyl-L-carnitine and free carnitine could be used as blood biomarkers to find people with Alzheimer's disease and maybe even people who are more likely to get dementia early," said Betty Bigio, PhD, lead investigator and research assistant professor at NYU Grossman School of Medicine and an affiliate of the Nathan Kline Institute for Psychiatric Research. "The findings may also explain why, as Alzheimer's disease progresses, the levels of acetyl-L-carnitine and free carnitine increase. This is why researchers believe that these metabolic pathways could serve as therapeutic targets for early intervention before irreparable brain damage occurs.

The researchers also revealed that healthy volunteers were comparable in age, weight, and education. The Californian group's findings supported the patterns observed in the Brazilian cohort. 

Researchers think that acetyl-L-carnitine and free carnitine levels could be therapeutic targets for early intervention before irreversible brain damage happens because they drop as Alzheimer's disease gets worse. Decreases in acetyl-L-carnitine and free carnitine were strongly associated with the severity of Alzheimer's disease. Carla Nasca, PhD, a senior investigator and assistant professor in the Neuroscience and Psychiatry departments at NYU Grossman School of Medicine, says that the molecular pathways that make them may be new therapeutic targets for finding the disease's cause and maybe stopping it before it does permanent damage to the brain. 

The main goals of future research will be to find the main sources of acetyl-L-carnitine, study the molecular pathways that control its production, and find out how this molecule changes the chemistry of the brain. If these findings are validated in future research, they could pave the way for the development of a non-invasive blood test for diagnosing dementia and tracking Alzheimer's progression. Current procedures rely on cerebrospinal fluid testing, which necessitates spinal taps and raises the possibility of discomfort and infection. A simple blood test may provide a more objective and quantitative assessment of sickness severity than existing cognitive evaluations that rely on memory and thinking abilities. 

A blood test could potentially assist in predicting the efficacy of future new medications aimed at delaying or preventing Alzheimer's disease. Both acetyl-L-carnitine and free carnitine are crucial for brain function and cellular energy metabolism. Nasca's team has previously discovered that acetyl-L-carnitine facilitates communication between a cell's mitochondria and nucleus. This regulates the genes that produce glutamate, a neurotransmitter involved in memory and brain plasticity. This function is especially crucial for the hippocampus, a brain region responsible for memory and one of the first areas affected by Alzheimer's disease. 

Furthermore, studies have linked mood disorders and severe depression, both closely related to Alzheimer's disease, to elevated glutamate levels. Nasca's research has also connected deficiencies in acetyl-L-carnitine, but not free carnitine, to depression and childhood trauma. These findings suggest that future research should focus on medicines that prevent depression from developing into Alzheimer's disease. 

This discovery is a significant step towards understanding the molecular underpinnings of Alzheimer's disease and identifying new pathways for early detection and treatment. Further research could confirm these blood signs, potentially altering Alzheimer's disease diagnosis, monitoring, and treatment.