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<p>Altered systemic metabolism contributes to Alzheimer’s disease (AD) pathology, yet the links between specific metabolites, cortical amyloid deposition, and cognition remain unclear. This study conducted targeted profiling of over 600 serum metabolites across 26 biochemical classes in 746 ADNI participants (CN = 248, MCI = 403, AD = 95), identifying propionylcarnitine and methionine as significantly associated metabolites. Relationships among these metabolites, cortical Aβ accumulation, and cognitive performance were examined using regression and mediation analyses, adjusting for age, sex, education, and APOE ε4 status. The results showed that serum propionylcarnitine and methionine levels did not differ across diagnostic groups. In AD participants, higher propionylcarnitine (β = − 0.24, FDR <i>p</i> = 0.019) and methionine (β = − 0.33, FDR <i>p</i> = 0.005) levels were associated with lower cerebellum-referenced cortical amyloid burden, whereas no significant associations were observed in CN or MCI individuals. Mediation analyses indicated that serum propionylcarnitine did not show significant indirect effects on cognitive performance via cortical amyloid burden in any group. For methionine, nominally significant indirect effects on cognition were observed in AD participants before FDR correction (ADAS-Cog 11: β = − 0.11, <i>p</i> = 0.040; ADAS-Cog 13: β = − 0.13, <i>p</i> = 0.044), but these did not remain significant after FDR adjustment (FDR <i>p</i> &gt; 0.19), suggesting modest, non-significant associations of methionine with cognitive performance via cortical amyloid burden, although these findings were observational and did not imply causation. In short, higher propionylcarnitine and methionine were linked to lower cortical Aβ accumulation in AD, highlighting future research directions to explore their mechanistic roles in AD pathology.</p>

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Higher Serum Levels of Propionylcarnitine and Methionine are Associated with Reduced Cortical Amyloid Burden in Alzheimer’s Disease

  • 期刊论文

  • 发表日期：

    2026年2月20日

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  • Qamar Abuhassan,
  • Ghaleb Oriquat,
  • Soumya V. Menon,
  • Laxmidhar Maharana,
  • L. Inbathamizh,
  • Gunjan Mukherjee,
  • Aashna Sinha,
  • Shokhjakhon Furkatov

摘要

Altered systemic metabolism contributes to Alzheimer’s disease (AD) pathology, yet the links between specific metabolites, cortical amyloid deposition, and cognition remain unclear. This study conducted targeted profiling of over 600 serum metabolites across 26 biochemical classes in 746 ADNI participants (CN = 248, MCI = 403, AD = 95), identifying propionylcarnitine and methionine as significantly associated metabolites. Relationships among these metabolites, cortical Aβ accumulation, and cognitive performance were examined using regression and mediation analyses, adjusting for age, sex, education, and APOE ε4 status. The results showed that serum propionylcarnitine and methionine levels did not differ across diagnostic groups. In AD participants, higher propionylcarnitine (β = − 0.24, FDR p = 0.019) and methionine (β = − 0.33, FDR p = 0.005) levels were associated with lower cerebellum-referenced cortical amyloid burden, whereas no significant associations were observed in CN or MCI individuals. Mediation analyses indicated that serum propionylcarnitine did not show significant indirect effects on cognitive performance via cortical amyloid burden in any group. For methionine, nominally significant indirect effects on cognition were observed in AD participants before FDR correction (ADAS-Cog 11: β = − 0.11, p = 0.040; ADAS-Cog 13: β = − 0.13, p = 0.044), but these did not remain significant after FDR adjustment (FDR p > 0.19), suggesting modest, non-significant associations of methionine with cognitive performance via cortical amyloid burden, although these findings were observational and did not imply causation. In short, higher propionylcarnitine and methionine were linked to lower cortical Aβ accumulation in AD, highlighting future research directions to explore their mechanistic roles in AD pathology.