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Cited by 27Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAdvanced Proteomics Techniques and Applications

Sequence of proteome profiles in preclinical and symptomatic Alzheimer's disease

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Li, Xiaohang, Tsolis, Konstantinos C., Koper, Marta J., Ronisz, Alicja, Ospitalieri, Simona, von Arnim, Christine A.F., Vandenberghe, Rik, Tousseyn, Thomas +5 more·2021·Alzheimer's & Dementia
DOI 10.1002/alz.12345
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Abstract

Proteome profile changes in Alzheimer's disease (AD) brains have been reported. However, it is unclear whether they represent a continuous process, or whether there is a sequential involvement of distinct proteins. To address this question, we used mass spectrometry. We analyzed soluble, dispersible, sodium dodecyl sulfate, and formic acid fractions of neocortex homogenates (mainly Brodmann area 17‐19) from 18 pathologically diagnosed preclinical AD, 17 symptomatic AD, and 18 cases without signs of neurodegeneration. By doing so, we identified four groups of AD‐related proteins being changed in levels in preclinical and symptomatic AD cases: early‐responding, late‐responding, gradually‐changing, and fraction‐shifting proteins. Gene ontology analysis of these proteins and all known AD‐risk/causative genes identified vesicle endocytosis and the secretory pathway‐related processes as an early‐involved AD component. In conclusion, our findings suggest that subtle changes involving the secretory pathway and endocytosis precede severe proteome changes in symptomatic AD as part of the preclinical phase of AD. The respective early‐responding proteins may also contribute to synaptic vesicle cycle alterations in symptomatic AD.

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  • Proteomics analyses of neocortex tissues from pathologically diagnosed preclinical AD cases revealed an increase in processes associated with vesicle endocytosis and the secretory pathway.

    “Interestingly, proteomics analyses of neocortex tissues from pathologically diagnosed preclinical AD cases revealed an increase in processes associated with vesicle endocytosis and the secretory pathway [54].”

    From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [54]

    Section 3.2 reports that vesicle-endocytosis and secretory-pathway terms were over-represented among early-responding proteins in neocortex samples. But the Study conclusions and disease implications section describes an early decrease in proteins associated with these pathways, not an increase in the processes themselves. The claim is supported as to the pathways identified, but not its stated direction of change. (LLM, conf=0.84)

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Authors
Li, X., Tsolis, K. C., Koper, M. J., Ronisz, A., Ospitalieri, S., von Arnim, C. A. F., Vandenberghe, R., Tousseyn, T., Scheuerle, A., Economou, A., Carpentier, S., Otto, M., & Thal, D. R.
Affiliations
  • KU Leuven (BE)
  • VIB-KU Leuven Center for Brain & Disease Research (BE)
  • Department of Neurology University of Ulm Ulm Germany
  • Universitair Ziekenhuis Leuven (BE)
  • Universität Ulm (DE)
  • BIOMED facility for SYstems BIOlogy based MAss spectrometry KU Leuven (University of Leuven) Leuven Belgium
Corresponding author
Thal, Dietmar Rudolf
ORCID
Venue
Alzheimer's & Dementia
Publisher
Wiley
Published
2021-04-19
Volume
17
Issue
6
Pages
946-958
ISSN
  • 1552-5260 (ISSN-L)
  • 1552-5279
DOI
10.1002/alz.12345
OpenAlex
W3156202211
Cited by
27
References
86
Citations by year
2026: 4 · 2025: 5 · 2024: 4 · 2023: 7 · 2022: 5 · 2021: 2
FWCI
2.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s & Dementia (publishedVersion)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
Funders
  • Deutsche Forschungsgemeinschaft (SFB 1279)
  • Bundesministerium für Bildung und Forschung (01ED1203F, 01ED1512, FTLDc 01GI1007A, 01GI1007A)
  • Fonds Wetenschappelijk Onderzoek (G065721N, G0H2116N, G0F8516N)
  • KU Leuven (RUN/16/001, /16/001)
  • Vlaamse regering (IWT135043, 135043)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
Alzheimer's disease, preclinical Alzheimer's disease
MeSH terms
Alzheimer Disease, Brain, Humans, Mass Spectrometry, Amyloid beta-Peptides, Neocortex, Proteome, Proteomics, Prodromal Symptoms

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