Decreased brain creatine levels in elderly apolipoprotein E epsilon 4 carriers

Area of Science:

• Neuroimaging
• Neurochemistry
• Genetics

Background:

• Apolipoprotein E (ApoE) genotype influences neuroimaging study outcomes.
• No in vivo data exists on ApoE-related changes observable by proton magnetic resonance spectroscopy (MRS).

Purpose of the Study:

• To investigate in vivo ApoE genotype-related differences in brain metabolites using proton magnetic resonance spectroscopy (MRS).
• To explore the relationship between ApoE genotype, brain creatine levels, and cognitive function in non-demented elderly individuals.

Main Methods:

• Proton magnetic resonance spectra were acquired from the occipital cortex of 22 non-demented elderly participants.
• Participants were genotyped for the ApoE epsilon4 allele (n=8 carriers, n=14 non-carriers).
• Absolute peak areas of N-acetyl aspartate, myo-inositol, choline, and creatine were measured.

Main Results:

• No significant differences in N-acetyl aspartate, myo-inositol, or choline levels were found between ApoE epsilon4 carriers and non-carriers.
• Creatine levels were significantly lower in ApoE epsilon4 carriers compared to non-carriers.
• Creatine levels correlated with age and Mini-Mental State Examination scores in epsilon4 carriers, but not in non-carriers.

Conclusions:

• ApoE epsilon4 allele is associated with reduced brain creatine levels, potentially indicating increased metabolic demands.
• Lower creatine levels in epsilon4 carriers may serve as an early indicator of incipient Alzheimer's disease.
• Creatine's potential neuroprotective effects warrant further investigation in the context of ApoE genotype and AD therapeutics.