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@ARTICLE{Zafar:282327,
author = {Zafar, Saima and Noor, Aneeqa and Younas, Neelam and
Shafiq, Mohsin and Dittmar, Kathrin and Yagensky, Oleksandr
and Schmitz, Matthias and Ferrer, Isidre and Hermann, Peter
and Zerr, Inga},
title = {{P}roteomic {P}rofiling {R}eveals {M}itochondrial
{D}ysregulation in {R}apidly {P}rogressive {A}lzheimer's:
{R}ole of {DLDH} in {A}myloid {B}eta {A}ggregation.},
journal = {Molecular neurobiology},
volume = {63},
number = {1},
issn = {0893-7648},
address = {Totowa, NJ},
publisher = {Humana Press},
reportid = {DZNE-2025-01288},
pages = {73},
year = {2025},
abstract = {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.},
keywords = {Humans / Alzheimer Disease: metabolism / Alzheimer Disease:
pathology / Amyloid beta-Peptides: metabolism / Proteomics:
methods / Mitochondria: metabolism / Mitochondria: pathology
/ Male / Female / Disease Progression / Aged / Protein
Aggregation, Pathological: metabolism / Brain: metabolism /
Brain: pathology / Protein Aggregates / Aged, 80 and over /
Alzheimer’s disease (AD) (Other) / DLDH (Other) /
Metabolic networks (Other) / Metabolism (Other) /
Post-translational modification (Other) / Proteomics (Other)
/ Rapidly progressive Alzheimer’s disease (rpAD) (Other) /
Amyloid beta-Peptides (NLM Chemicals) / Protein Aggregates
(NLM Chemicals)},
cin = {AG Zerr},
ddc = {570},
cid = {I:(DE-2719)1440011-1},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41254340},
doi = {10.1007/s12035-025-05327-0},
url = {https://pub.dzne.de/record/282327},
}