A seven-year longitudinal study of the Alzheimer's disease metabolome.

In 1,430 ADNI participants, 311 of 506 serum metabolites are significantly associated with 15 Alzheimer’s disease phenotypes, with 128 showing persistent links over time.

• Why it matters: Metabolic dysregulation is a hallmark of Alzheimer’s disease, but it is unclear when these serum changes emerge relative to clinical and endophenotypic progression.
• What they did: Using cross-sectional single-timepoint, joint multi-timepoint, and time-interaction analyses on 4,063 longitudinal serum samples, the study tested metabolite–phenotype associations across 15 AD-related outcomes.
• The result: Most associated metabolites reflect fatty acid and energy metabolism, neurotransmitter pathways, and oxidative stress regulation and remain stable once established, while only a small subset (including betaine, choline, and few amino acids) shows steeper declines with worsening endophenotypes.

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