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Alterations of human CSF and serum-based mitophagy biomarkers in the continuum of Alzheimer disease. | LitMetric

AI Article Synopsis

  • This study investigates mitophagy impairment in Alzheimer's disease (AD) by examining biomarkers in serum and cerebrospinal fluid (CSF) from 246 individuals, including those with mild cognitive impairment (MCI-AD), AD dementia, and cognitively unimpaired individuals.
  • The results indicate that certain biomarkers (PINK1, BNIP3L, TFEB) were differently expressed in individuals with AD compared to those who were cognitively unimpaired, suggesting a link between mitophagy impairment and AD pathology.
  • Moreover, the levels of these biomarkers correlated with cognitive function and clinical indicators of AD severity, highlighting the potential of mitophagy biomarkers as indicators for disease progression.

Article Abstract

Defective mitophagy is consistently found in postmortem brain and iPSC-derived neurons from Alzheimer disease (AD) patients. However, there is a lack of extensive examination of mitophagy status in serum or cerebrospinal fluid (CSF), and the clinical potential of mitophagy biomarkers has not been tested. We quantified biomarkers of mitophagy/autophagy and lysosomal degradation (PINK1, BNIP3L and TFEB) in CSF and serum from 246 individuals, covering mild cognitive impairment due to AD (MCI-AD,  = 100), dementia due to AD (AD-dementia,  = 100), and cognitively unimpaired individuals (CU,  = 46), recruited from the Czech Brain Aging Study. Cognitive function and brain atrophy were also assessed. Our data show that serum and CSF PINK1 and serum BNIP3L were higher, and serum TFEB was lower in individuals with AD than in corresponding CU individuals. Additionally, the magnitude of mitophagy impairment correlated with the severity of clinical indicators in AD patients. Specifically, levels of PINK1 positively correlated with phosphorylated (p)-MAPT/tau (181), total (t)-MAPT/tau, NEFL (neurofilament light chain), and NRGN (neurogranin) levels in CSF and negatively with memory, executive function, and language domain. Serum TFEB levels negatively correlated with NEFL and positively with executive function and language. This study reveals mitophagy impairment reflected in biofluid biomarkers of individuals with AD and associated with more advanced AD pathology. Aβ: amyloid beta; AD: Alzheimer disease; AVs: autophagic vacuoles; BNIP3L: BCL2 interacting protein 3 like; CU: cognitively unimpaired; CSF: cerebrospinal fluid; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCI: mild cognitive impairment; NRGN: neurogranin; NEFL: neurofilament light chain; p-MAPT/tau: phosphorylated microtubule associated protein tau; PINK1: PTEN induced kinase 1; t-MAPT/tau: total microtubule associated protein tau; TFEB: transcription factor EB; TMT: Trail Making Test.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11262225PMC
http://dx.doi.org/10.1080/15548627.2024.2340408DOI Listing

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