Mitochondrial alterations in fibroblasts from sporadic Alzheimer's disease (AD) patients correlate with AD-related clinical hallmarks.
Acta Neuropathol Commun
; 12(1): 90, 2024 06 08.
Article
de En
| MEDLINE
| ID: mdl-38851733
ABSTRACT
Mitochondrial dysfunctions are key features of Alzheimer's disease (AD). The occurrence of these disturbances in the peripheral cells of AD patients and their potential correlation with disease progression are underinvestigated. We studied mitochondrial structure, function and mitophagy in fibroblasts from healthy volunteers and AD patients at the prodromal (AD-MCI) or demented (AD-D) stages. We carried out correlation studies with clinical cognitive scores, namely, (i) Mini-Mental State Examination (MMSE) and (ii) Dementia Rating-Scale Sum of Boxes (CDR-SOB), and with (iii) amyloid beta (Aß) plaque burden (PiB-PET imaging) and (iv) the accumulation of peripheral amyloid precursor protein C-terminal fragments (APP-CTFs). We revealed alterations in mitochondrial structure as well as specific mitochondrial dysfunction signatures in AD-MCI and AD-D fibroblasts and revealed that defective mitophagy and autophagy are linked to impaired lysosomal activity in AD-D fibroblasts. We reported significant correlations of a subset of these dysfunctions with cognitive decline, AD-related clinical hallmarks and peripheral APP-CTFs accumulation. This study emphasizes the potential use of peripheral cells for investigating AD pathophysiology.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maladie d'Alzheimer
/
Fibroblastes
/
Mitophagie
/
Mitochondries
Limites:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
Acta Neuropathol Commun
Année:
2024
Type de document:
Article
Pays d'affiliation:
France