Abstract
This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer’s disease. Twenty-nine patients with probable Alzheimer’s disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer’s disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer’s disease group; and subjective memory complaint vs. Alzheimer’s disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer’s disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer’s disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer’s disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal study is needed before application to clinical practice.
Highlights
Among the major challenges of modern research there are the treatment and prevention of Alzheimer's disease (AD), the most common and fearsome form of dementia
Pairwise multiple comparisons showed that HS was significantly different from subjective memory complaint (SMC) (p
While the comparison HS vs. AD was significant for all such acyl-carnitines, the comparison MCI vs. HS was significant for C10, C12:1, C14:1, C16:1, C18 and C18:1, and the comparison HS vs. SMC for C16:1 and C18
Summary
Among the major challenges of modern research there are the treatment and prevention of Alzheimer's disease (AD), the most common and fearsome form of dementia. Researches, focusing on the characterization of the earliest, preclinical stages of dementia, identified transitional states between normal aging and AD, known as mild cognitive impairment (MCI) and subjective memory complaint (SMC). MCI refers to the clinical condition in which persons experience memory loss and/or other cognitive impairments greater than expected for age and level of education, but they do not fulfill accepted criteria for dementia. This condition is at high risk for developing AD and is suitable for possible therapeutic intervention [1, 2]. The subjects with MCI and/or SMC should be identified and possibly treated to prevent the progression to dementia
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