TY  - JOUR
AU  - Zafar, Saima
AU  - Noor, Aneeqa
AU  - Younas, Neelam
AU  - Shafiq, Mohsin
AU  - Dittmar, Kathrin
AU  - Yagensky, Oleksandr
AU  - Schmitz, Matthias
AU  - Ferrer, Isidre
AU  - Hermann, Peter
AU  - Zerr, Inga
TI  - Proteomic Profiling Reveals Mitochondrial Dysregulation in Rapidly Progressive Alzheimer's: Role of DLDH in Amyloid Beta Aggregation.
JO  - Molecular neurobiology
VL  - 63
IS  - 1
SN  - 0893-7648
CY  - Totowa, NJ
PB  - Humana Press
M1  - DZNE-2025-01288
SP  - 73
PY  - 2025
AB  - Alzheimer's disease (AD) is presented as multiple clinical variants depending upon the rate of progression and familial background; however, the exact molecular mechanisms associated with these subtypes and their treatments are yet to be understood. The current study is based on a global proteome analysis of brain samples from patients (n = 38) with rapidly progressive AD (rpAD-survival time < 3 years), sporadic AD (spAD-survival time of 8-10 years), and healthy controls. Proteome analysis revealed a differential regulation of 79 proteins and highlighted the dysregulation of mitochondrial machinery and glucose metabolism in rpAD. Dihydrolipoamide dehydrogenase (DLDH), a mitochondrial oxidoreductase, showed a significant reduction and delocalization in rpAD. In vitro analysis revealed a potential role of DLDH in the aggregation of amyloid beta. Rapid progression in AD may be influenced by the energy homeostasis and redox dysfunction linked with the DLDH.
KW  - Humans
KW  - Alzheimer Disease: metabolism
KW  - Alzheimer Disease: pathology
KW  - Amyloid beta-Peptides: metabolism
KW  - Proteomics: methods
KW  - Mitochondria: metabolism
KW  - Mitochondria: pathology
KW  - Male
KW  - Female
KW  - Disease Progression
KW  - Aged
KW  - Protein Aggregation, Pathological: metabolism
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - Protein Aggregates
KW  - Aged, 80 and over
KW  - Alzheimer’s disease (AD) (Other)
KW  - DLDH (Other)
KW  - Metabolic networks (Other)
KW  - Metabolism (Other)
KW  - Post-translational modification (Other)
KW  - Proteomics (Other)
KW  - Rapidly progressive Alzheimer’s disease (rpAD) (Other)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Protein Aggregates (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41254340
DO  - DOI:10.1007/s12035-025-05327-0
UR  - https://pub.dzne.de/record/282327
ER  -