Dataset Information

Mitochondrial DNA and Inflammation in Alzheimer's Disease.

ABSTRACT: Mitochondrial dysfunction and neuroinflammation are implicated in the pathogenesis of most neurodegenerative diseases, such as Alzheimer's disease (AD). In fact, although a growing number of studies show crosstalk between these two processes, there remain numerous gaps in our knowledge of the mechanisms involved, which requires further clarification. On the one hand, mitochondrial dysfunction may lead to the release of mitochondrial damage-associated molecular patterns (mtDAMPs) which are recognized by microglial immune receptors and contribute to neuroinflammation progression. On the other hand, inflammatory molecules released by glial cells can influence and regulate mitochondrial function. A deeper understanding of these mechanisms may help identify biomarkers and molecular targets useful for the treatment of neurodegenerative diseases. This review of works published in recent years is focused on the description of the mitochondrial contribution to neuroinflammation and neurodegeneration, with particular attention to mitochondrial DNA (mtDNA) and AD.

SUBMITTER: Galizzi G

PROVIDER: S-EPMC10670154 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Mitochondrial DNA and Inflammation in Alzheimer's Disease.

Galizzi Giacoma G Di Carlo Marta M

Current issues in molecular biology 20231025 11

Mitochondrial dysfunction and neuroinflammation are implicated in the pathogenesis of most neurodegenerative diseases, such as Alzheimer's disease (AD). In fact, although a growing number of studies show crosstalk between these two processes, there remain numerous gaps in our knowledge of the mechanisms involved, which requires further clarification. On the one hand, mitochondrial dysfunction may lead to the release of mitochondrial damage-associated molecular patterns (mtDAMPs) which are recogn ...[more]

PMID: 37998717

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Project description:Alzheimer's type dementia (AD) exhibits clinical heterogeneity, as well as differences in disease progression, as a subset of patients with a clinical diagnosis of AD progresses more rapidly (rpAD) than the typical AD of slow progression (spAD). Previous findings indicate that low cerebrospinal fluid (CSF) content of cell-free mitochondrial DNA (cf-mtDNA) precedes clinical signs of AD. We have now investigated the relationship between cf-mtDNA and other biomarkers of AD to determine whether a particular biomarker profile underlies the different rates of AD progression. We measured the content of cf-mtDNA, beta-amyloid peptide 1-42 (Aβ), total tau protein (t-tau) and phosphorylated tau (p-tau) in the CSF from a cohort of 95 subjects consisting of 49 controls with a neurologic disorder without dementia, 30 patients with a clinical diagnosis of spAD and 16 patients with rpAD. We found that 37% of controls met at least one AD biomarker criteria, while 53% and 44% of subjects with spAD and rpAD, respectively, did not fulfill the two core AD biomarker criteria: high t-tau and low Aβ in CSF. In the whole cohort, patients with spAD, but not with rpAD, showed a statistically significant 44% decrease of cf-mtDNA in CSF compared to control. When the cohort included only subjects selected by Aβ and t-tau biomarker criteria, the spAD group showed a larger decrease of cf-mtDNA (69%), whereas in the rpAD group cf-mtDNA levels remained unaltered. In the whole cohort, the CSF levels of cf-mtDNA correlated positively with Aβ and negatively with p-tau. Moreover, the ratio between cf-mtDNA and p-tau increased the sensitivity and specificity of spAD diagnosis up to 93% and 94%, respectively, in the biomarker-selected cohort. These results show that the content of cf-mtDNA in CSF correlates with the earliest pathological markers of the disease, Aβ and p-tau, but not with the marker of neuronal damage t-tau. Moreover, these findings confirm that low CSF content of cf-mtDNA is a biomarker for the early detection of AD and support the hypothesis that low cf-mtDNA, together with low Aβ and high p-tau, constitute a distinctive CSF biomarker profile that differentiates spAD from other neurological disorders.

Dataset Information

Mitochondrial DNA and Inflammation in Alzheimer's Disease.

Publications

Mitochondrial DNA and Inflammation in Alzheimer's Disease.

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