%0 Journal Article
%A Zafar, Saima
%A Noor, Aneeqa
%A Younas, Neelam
%A Shafiq, Mohsin
%A Dittmar, Kathrin
%A Yagensky, Oleksandr
%A Schmitz, Matthias
%A Ferrer, Isidre
%A Hermann, Peter
%A Zerr, Inga
%T Proteomic Profiling Reveals Mitochondrial Dysregulation in Rapidly Progressive Alzheimer's: Role of DLDH in Amyloid Beta Aggregation.
%J Molecular neurobiology
%V 63
%N 1
%@ 0893-7648
%C Totowa, NJ
%I Humana Press
%M DZNE-2025-01288
%P 73
%D 2025
%X 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.
%K Humans
%K Alzheimer Disease: metabolism
%K Alzheimer Disease: pathology
%K Amyloid beta-Peptides: metabolism
%K Proteomics: methods
%K Mitochondria: metabolism
%K Mitochondria: pathology
%K Male
%K Female
%K Disease Progression
%K Aged
%K Protein Aggregation, Pathological: metabolism
%K Brain: metabolism
%K Brain: pathology
%K Protein Aggregates
%K Aged, 80 and over
%K Alzheimer’s disease (AD) (Other)
%K DLDH (Other)
%K Metabolic networks (Other)
%K Metabolism (Other)
%K Post-translational modification (Other)
%K Proteomics (Other)
%K Rapidly progressive Alzheimer’s disease (rpAD) (Other)
%K Amyloid beta-Peptides (NLM Chemicals)
%K Protein Aggregates (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41254340
%R 10.1007/s12035-025-05327-0
%U https://pub.dzne.de/record/282327