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Cited by 188S100 Proteins and AnnexinsAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

S100 Proteins in Alzheimer’s Disease

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Cristóvão, Joana S., Gomes, Cláudio M.·2019·Frontiers in Neuroscience
DOI 10.3389/fnins.2019.00463PMC PMC6532343
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Abstract

S100 proteins are calcium-binding proteins that regulate several processes associated with Alzheimer's disease (AD) but whose contribution and direct involvement in disease pathophysiology remains to be fully established. Due to neuroinflammation in AD patients, the levels of several S100 proteins are increased in the brain and some S100s play roles related to the processing of the amyloid precursor protein, regulation of amyloid beta peptide (Aβ) levels and Tau phosphorylation. S100 proteins are found associated with protein inclusions, either within plaques or as isolated S100-positive puncta, which suggests an active role in the formation of amyloid aggregates. Indeed, interactions between S100 proteins and aggregating Aβ indicate regulatory roles over the aggregation process, which may either delay or aggravate aggregation, depending on disease stage and relative S100 and Aβ levels. Additionally, S100s are also known to influence AD-related signaling pathways and levels of other cytokines. Recent evidence also suggests that metal-ligation by S100 proteins influences trace metal homeostasis in the brain, particularly of zinc, which is also a major deregulated process in AD. Altogether, this evidence strongly suggests a role of S100 proteins as key players in several AD-linked physiopathological processes, which we discuss in this review.

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  • S100A12 is a pro-inflammatory protein localized within Aβ plaques.

    “For instance, S100A12 is a pro‐inflammatory protein localized within Aβ plaques. 59 , 77”

    From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [77]

    The S100A12 section reports S100A12 hexamers associated with senile plaques in AD brains, and the Outlook says S100A12 is found within amyloid plaques. The S100 Protein Family section describes pro-inflammatory activity for some S100 proteins, but the copy does not establish that activity specifically for S100A12. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Cristóvão, J. S., & Gomes, C. M.
Affiliations
University of Lisbon (PT)
Corresponding author
Gomes, Cláudio M.
ORCID
Venue
Frontiers in Neuroscience
Publisher
Frontiers Media SA
Published
2019-05-16
Volume
13
Pages
463-463
ISSN
1662-453X (ISSN-L)
DOI
10.3389/fnins.2019.00463
PMC
PMC6532343
OpenAlex
W2945404218
Cited by
188
References
10
Citations by year
2026: 19 · 2025: 29 · 2024: 34 · 2023: 26 · 2022: 39 · 2021: 24 · 2020: 13 · 2019: 4
FWCI
1.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Fundação para a Ciência e a Tecnologia (PTDC/NEU-NMC/2138/2014, IF/01046/2014, UID/Multi/04046/2013)
  • Fundação Bial (PT/FB/BL-2014-343)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
S-100 protein, Alzheimer's disease, calcium-binding proteins, neuroinflammation, APP processing, amyloid-beta aggregation, tau phosphorylation, amyloid plaques, trace metal homeostasis, zinc, cytokines, disease pathophysiology

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