Study Advances Possible Blood Test for Early-Stage Alzheimer's Disease

An estimated six million Americans, predominantly women over the age of 65, are currently living with some form of Alzheimer's disease. A new study has found that declining blood levels of two naturally occurring molecules are closely linked to the progression of Alzheimer's, particularly in women. These molecules were found to decrease gradually, starting from women without signs of memory problems, disorientation, or slowed thinking, to those with early signs of mild cognitive impairment. Published in the journal Molecular Psychiatry, the study found that the decreases were more pronounced in women with moderate or severe stages of the disease, while in men, declines were observed in only one of the molecules, highlighting a disease-specific difference between the sexes.

The study, led by neuroscientists at NYU Langone Health (New York City, NY, USA) in collaboration with other researchers from the U.S. and Brazil, showed that blood levels of the protein acetyl-L-carnitine were lower in both women and men with mild cognitive impairment and Alzheimer's disease. The study also found that blood levels of free carnitine, a primary byproduct of acetyl-L-carnitine essential to brain function, declined steadily in women, with the amount of decline correlating to the severity of cognitive impairment. In contrast, significant declines were seen in men only for acetyl-L-carnitine, not free carnitine. The results suggest that reductions in these two brain chemicals could indicate both the presence and severity of Alzheimer's disease, potentially explaining why women are at a higher risk of developing the disease compared to men. Further analysis showed that blood levels of acetyl-L-carnitine and free carnitine directly aligned with increased levels of amyloid beta and tangled tau proteins, which are established markers of Alzheimer's progression.

The study’s diagnostic accuracy increased from over 80%—when using either amyloid beta and tau protein levels from cerebrospinal fluid or the two blood molecules—to 93% when both sets of data were used. The research team believes more investigation is needed to understand the sources of acetyl-L-carnitine and the molecular pathways controlling its production, as well as how the molecule affects brain chemistry when released into the blood from brain vesicle stores. The team’s long-term goal is to identify other biomarkers that closely track Alzheimer's disease progression. If their findings are confirmed by further studies, this research could lead to the development of a blood test for dementia and for monitoring Alzheimer's progression in a more convenient, noninvasive manner. Currently, identifying biomarkers of disease progression often requires multiple spinal taps, which carry risks of pain and infection. A blood test could provide a more objective, quantitative measure of disease severity, supplementing or even replacing existing memory and cognitive tests. Moreover, it could help predict the effectiveness of potential drug treatments aimed at delaying or preventing Alzheimer's onset.

"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," said study lead investigator Betty Bigio, PhD.

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