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, n = 100), dementia due to AD (AD-dementia, n = 100), and cognitively unimpaired individuals (CU, n = 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.Abbreviation: 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.

• Klíčová slova
• Autophagy, BNIP3L, PINK1, TFEB, mild cognitive impairment, mitophagy,
• MeSH
• Alzheimerova nemoc * mozkomíšní mok   krev   diagnóza   MeSH
• biologické markery * mozkomíšní mok   krev   metabolismus   MeSH
• kognitivní dysfunkce mozkomíšní mok   krev   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny mozkomíšní mok   metabolismus   krev   MeSH
• mitofagie * MeSH
• mozek metabolismus   patologie   MeSH
• nádorové supresorové proteiny MeSH
• proteinkinasy metabolismus   MeSH
• proteiny tau mozkomíšní mok   metabolismus   MeSH
• protoonkogenní proteiny mozkomíšní mok   krev   metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkripční faktory BHLH-Zip metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery * MeSH
• BNIP3L protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• nádorové supresorové proteiny MeSH
• proteinkinasy MeSH
• proteiny tau MeSH
• protoonkogenní proteiny MeSH
• PTEN-induced putative kinase MeSH Prohlížeč
• TFEB protein, human MeSH Prohlížeč
• transkripční faktory BHLH-Zip MeSH