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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. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that motor rehabilitation may delay Parkinson's disease (PD) progression. Moreover, parallel treatments in animals up-regulate brain-derived neurotrophic factor (BDNF). Thus, we investigated the effect of a motor rehabilitation protocol on PD symptoms and BDNF serum levels. Motor rehabilitation training consisted of a cycle of 20 days/ month of physiotherapy divided in 3 daily sessions. Clinical data were collected at the beginning, at the end, and at 90 days follow-up. BDNF serum levels were detected by ELISA at 0, 7, 14, 21, 30, and 90 days. The follow-up period had a duration of 60 days (T30-T90). The results showed that at the end of the treatment (day 30), an improvement in extrapyramidal signs (UPDRS III; UPDRS III - Gait and Balance items), motor (6 Minute Walking Test), and daily living activities (UPDRS II; PDQ-39) was observed. BDNF levels were increased at day 7 as compared with baseline. After that, no changes in BDNF were observed during the treatment and in the successive follow-up. This study demonstrates that motor rehabilitation training is able to ameliorate PD symptoms and to increase temporarily BDNF serum levels. The latter effect may potentially contribute to the therapeutic action. Key words: motor rehabilitation, physical exercise, BDNF, Parkinson's disease. De plus en plus de donnees suggerent que la reeducation motrice peut retarder la progression de la maladie de Parkinson (MP). De plus, des traitements paralleles chez l'animal regulent a la hausse l'expression du facteur de croissance neurotrophique derive du cerveau BDNF. Ainsi, les auteurs ont etudie l'effet d'un protocole de reeducation motrice sur les symptomes de la MP et sur les niveaux seriques de BDNF. La reeducation motrice consistait en un cycle de 20 jours/mois de physiotherapie repartie en 3 sessions quotidiennes. Les donnees cliniques ont ete recoltees au debut, a la fin et au jour 90 en post-observation. Les niveaux seriques de BDNF ont ete mesures par ELISA a 0, 7,14, 30 et 90 jours. La periode post- observation avait une duree de 60 jours, (J30 cl J90). Les resultats ont montre qu'a la fin du traitement (J30), une amelioration des signes extrapyramidaux (echelle UPDRS III ; les items demarche et equilibre de l'echelle UPDRS III), des activites motrices (marche de 6 minutes) et quotidiennes (echelle UPDRS II; questionnaire PDQ-39) etait observee. Les niveaux de BDNF augmentaient au jour 7 comparativement au niveau de base, apres quoi, aucun changement des niveaux de BDNF n'etait observe durant le traitement et lors de la periode post-observation subsequente. Cette etude demontre que la reeducation motrice peut ameliorer les symptomes de la MP et accroitre temporairement les niveaux seriques de BDNF. Ce dernier effet peut potentiellement contribuer a l'action therapeutique observee. [Traduit par la Redaction] Mots-cles: reeducation motrice, exercice physique, BDNF, maladie de Parkinson., Introduction Parkinson's disease (PD) is a chronic neurodegenerative disease leading to motor dysfunctions characterized by resting tremor, bradykinesia, rigidity, and postural instability (Gazewood et al. 2013). PD is caused by [...]