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Observational Study
. 2025 Jul;106(1):38-43.
doi: 10.1177/13872877251337773. Epub 2025 Jun 12.

Circulating short chain fatty acids in Alzheimer's disease: A cross-sectional observational study

Moira Marizzoni  1 , Luigi Coppola  2 , Cristina Festari  3 , Delia Luongo  4 , Dominic Salamone  5 , Daniele Naviglio  6 , Andrea Soricelli  2 , Peppino Mirabelli  7 , Marco Salvatore  2 , Annamaria Cattaneo  1   8 , Giovanni B Frisoni  9
Affiliations
Observational Study

Circulating short chain fatty acids in Alzheimer's disease: A cross-sectional observational study

Moira Marizzoni et al. J Alzheimers Dis. 2025 Jul.

Abstract

Short chain fatty acids (SCFAs), produced mainly by gut microbes, might play a role in the pathophysiology of Alzheimer's disease (AD). We examined the SCFAs profile in 28 individuals with cognitive impairment due to AD (CI-AD), 29 with cognitive impairment not due to AD (CI-NAD), and 10 cognitively unimpaired (CU). CI-AD showed higher levels of acetate and valerate and lower levels of butyrate than CU and CI-NAD (p < 0.018). Acetate separated CI-AD from CI-NAD with AUC = 0.95 while the best neurodegeneration-related biomarker was GFAP with AUC = 0.79. SCFAs use for diagnosis and as treatment target in AD deserve further studies.

Keywords: Alzheimer's disease; cognitive impairment; microbiota-gut-brain axis; short chain fatty acids.

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Conflict of interest statement

Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Plasma SCFA profile distinguished Alzheimer's individuals from CI-NAD and CU. Plasma SCFAs and their ratios (A). Association matrices between SCFAs and peripheral neurodegeneration-related biomarkers (B). Discriminative power of SCFAs and their ratios (C), and comparison between the best discriminative SCFA versus peripheral biomarkers with good evidence of validity for the AD diagnosis (D). CU: cognitively unimpaired persons; CI-NAD: patients with cognitive impairment not due to AD; CI-AD: patients with cognitive impairment due to AD.
See this image and copyright information in PMC

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