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<p>A significant body of evidence suggests that mitochondrial dysfunction plays a key role in the development and progression of Alzheimer’s disease (AD). However, the absence of peripheral biomarkers for mitochondrial dysfunction limits its clinical applicability. Mitochondrial DNA (mtDNA) copy number, a proxy for mitochondrial function, has shown promise in detecting early stages of AD and predicting AD risk in cerebrospinal fluid (CSF) and blood, respectively. Surprisingly, recent studies have identified mtDNA molecules in human saliva, but their relationship with AD remains unexplored. Here, we investigated potential associations between salivary mtDNA copy number and cortical amyloid-β (Aβ) load measured with PET, and blood AD markers measured with ultrasensitive single molecule array (SIMOA) assays, in cognitively normal older adults. We found that salivary mtDNA copy number was positively correlated with cortical Aβ burden and plasma levels of tau phosphorylated at threonine 181 (pTau-181), and negatively correlated with general cognitive ability. It is worth noting that salivary mtDNA was not significantly associated with other blood-based AD biomarkers, including Aβ<sub>1-40</sub>, Aβ<sub>1-42</sub>, neurofilament-light chain (NfL), or glial fibrillary acidic protein (GFAP). Additionally, plasma pTau-181 levels moderated the association between salivary mtDNA and Aβ accumulation in the inferior temporal lobe, while Aβ load in the occipital cortex mediated the association between plasma pTau-181 and salivary mtDNA. Together, these findings represent the first evidence linking salivary mtDNA to well-established AD biomarkers in normal aging, suggesting that salivary mtDNA may serve as a potential non-invasive biomarker for identifying individuals at risk for developing AD in the general population.</p>

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Salivary mitochondrial DNA is associated with biomarkers of Alzheimer’s disease in cognitively normal older adults

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月6日

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  • Jose L. Cantero,
  • Mercedes Atienza,
  • Petar Podlesniy,
  • Margalida Puigròs,
  • Ramon Trullas

摘要

A significant body of evidence suggests that mitochondrial dysfunction plays a key role in the development and progression of Alzheimer’s disease (AD). However, the absence of peripheral biomarkers for mitochondrial dysfunction limits its clinical applicability. Mitochondrial DNA (mtDNA) copy number, a proxy for mitochondrial function, has shown promise in detecting early stages of AD and predicting AD risk in cerebrospinal fluid (CSF) and blood, respectively. Surprisingly, recent studies have identified mtDNA molecules in human saliva, but their relationship with AD remains unexplored. Here, we investigated potential associations between salivary mtDNA copy number and cortical amyloid-β (Aβ) load measured with PET, and blood AD markers measured with ultrasensitive single molecule array (SIMOA) assays, in cognitively normal older adults. We found that salivary mtDNA copy number was positively correlated with cortical Aβ burden and plasma levels of tau phosphorylated at threonine 181 (pTau-181), and negatively correlated with general cognitive ability. It is worth noting that salivary mtDNA was not significantly associated with other blood-based AD biomarkers, including Aβ1-40, Aβ1-42, neurofilament-light chain (NfL), or glial fibrillary acidic protein (GFAP). Additionally, plasma pTau-181 levels moderated the association between salivary mtDNA and Aβ accumulation in the inferior temporal lobe, while Aβ load in the occipital cortex mediated the association between plasma pTau-181 and salivary mtDNA. Together, these findings represent the first evidence linking salivary mtDNA to well-established AD biomarkers in normal aging, suggesting that salivary mtDNA may serve as a potential non-invasive biomarker for identifying individuals at risk for developing AD in the general population.