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Author Spotlight: Decoding Mitochondrial Aging
Published on: June 30, 2023
Mitochondrial DNA differentiates Alzheimer's disease from Creutzfeldt-Jakob disease
Petar Podlesniy1, Franc Llorens2, Ewa Golanska3
1Neurobiology Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas (CSIC), Barcelona, Spain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain.
Introduction:
Low content of cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a biomarker of early stage Alzheimer's disease (AD), but whether mtDNA is altered in a rapid neurodegenerative dementia such as Creutzfeldt-Jakob disease is unknown.
Methods:
CSF mtDNA was measured using digital polymerase chain reaction (dPCR) in two independent cohorts comprising a total of 112 patients diagnosed with sporadic Creutzfeldt-Jakob disease (sCJD), probable AD, or non-Alzheimer's type dementia.
Results:
Patients with AD exhibit low mtDNA content in CSF compared with patients diagnosed with sCJD or with non-Alzheimer's type dementias. The CSF concentration of mtDNA does not correlate with Aβ, t-tau, p-tau, and 14-3-3 protein levels in CSF.
Discussion:
Low-CSF mtDNA is not a consequence of brain damage and allows the differential diagnosis of AD from sCJD and other dementias. These results support the hypothesis that mtDNA in CSF is a pathophysiological biomarker of AD.
Insights
Low cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) can distinguish Alzheimer's disease (AD) from Creutzfeldt-Jakob disease (CJD) and other dementias. This finding supports mtDNA as a diagnostic biomarker for AD.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Low cell-free mitochondrial DNA (mtDNA) in cerebrospinal fluid (CSF) is a known biomarker for early-stage Alzheimer's disease (AD).
- The role of CSF mtDNA in rapid neurodegenerative dementias like Creutzfeldt-Jakob disease (CJD) remains uninvestigated.
Purpose of the Study:
- To investigate alterations in CSF mtDNA levels in patients with sporadic CJD (sCJD) compared to AD and other dementias.
- To determine if CSF mtDNA can serve as a differential diagnostic biomarker for AD.
Main Methods:
- Quantitative measurement of CSF mtDNA using digital polymerase chain reaction (dPCR).
- Analysis of two independent patient cohorts totaling 112 individuals diagnosed with sCJD, probable AD, or non-AD dementias.
Main Results:
- Patients with AD showed significantly lower CSF mtDNA content compared to patients with sCJD and non-AD dementias.
- CSF mtDNA concentration did not correlate with established AD biomarkers such as Aβ, t-tau, p-tau, and 14-3-3 protein levels.
Conclusions:
- Low CSF mtDNA is not solely a consequence of general brain damage and is a specific indicator differentiating AD from sCJD and other dementias.
- These findings support the hypothesis that CSF mtDNA is a pathophysiological biomarker for Alzheimer's disease.
