Journal Article

DZNE-2025-01288

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Proteomic Profiling Reveals Mitochondrial Dysregulation in Rapidly Progressive Alzheimer's: Role of DLDH in Amyloid Beta Aggregation.

Zafar, S.Extern* ; Noor, A. ; Younas, N.DZNE* ; Shafiq, M.DZNE* ; Dittmar, K.DZNE* ; Yagensky, O. ; Schmitz, M.DZNE* ; Ferrer, I. ; Hermann, P.DZNE* ; Zerr, I. (Last author)DZNE*

2025
Humana Press Totowa, NJ

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Please use a persistent id in citations: doi:10.1007/s12035-025-05327-0

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.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Proteomics: methods (MeSH) ; Mitochondria: metabolism (MeSH) ; Mitochondria: pathology (MeSH) ; Male (MeSH) ; Female (MeSH) ; Disease Progression (MeSH) ; Aged (MeSH) ; Protein Aggregation, Pathological: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Brain: pathology (MeSH) ; Protein Aggregates (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer’s disease (AD) ; DLDH ; Metabolic networks ; Metabolism ; Post-translational modification ; Proteomics ; Rapidly progressive Alzheimer’s disease (rpAD) ; Amyloid beta-Peptides ; Protein Aggregates

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Contributing Institute(s):

1. Translational Studies and Biomarker (AG Zerr)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DEAL Springer ; DEAL Springer ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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