Thiophene-Based Ligands for Specific Assignment of Distinct Aβ Pathologies in Alzheimer's Disease Article Swipe
Therése Klingstedt
,
Linda Lantz
,
Hamid Shirani
,
Junyue Ge
,
Jörg Hanrieder
,
Rubén Vidal
,
Bernardino Ghetti
,
K. Peter R. Nilsson
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1021/acschemneuro.4c00021
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1021/acschemneuro.4c00021
Aggregated species of amyloid-β (Aβ) are one of the pathological hallmarks in Alzheimer's disease (AD), and ligands that selectively target different Aβ deposits are of great interest. In this study, fluorescent thiophene-based ligands have been used to illustrate the features of different types of Aβ deposits found in AD brain tissue. A dual-staining protocol based on two ligands, HS-276 and LL-1, with different photophysical and binding properties, was developed and applied on brain tissue sections from patients affected by sporadic AD or familial AD associated with the PSEN1 A431E mutation. When binding to Aβ deposits, the ligands could easily be distinguished for their different fluorescence, and distinct staining patterns were revealed for these two types of AD. In sporadic AD, HS-276 consistently labeled all immunopositive Aβ plaques, whereas LL-1 mainly stained cored and neuritic Aβ deposits. In the PSEN1 A431E cases, each ligand was binding to specific types of Aβ plaques. The ligand-labeled Aβ deposits were localized in distinct cortical layers, and a laminar staining pattern could be seen. Biochemical characterization of the Aβ aggregates in the individual layers also showed that the variation of ligand binding properties was associated with certain Aβ peptide signatures. For the PSEN1 A431E cases, it was concluded that LL-1 was binding to cotton wool plaques, whereas HS-276 mainly stained diffuse Aβ deposits. Overall, our findings showed that a combination of ligands was essential to identify distinct aggregated Aβ species associated with different forms of AD.
Related Topics
Concepts
PSEN1
Ligand (biochemistry)
Staining
Senile plaques
Alzheimer's disease
Chemistry
Pathology
Amyloid (mycology)
Biology
Molecular biology
Biochemistry
Receptor
Amyloid precursor protein
Disease
Medicine
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1021/acschemneuro.4c00021
- https://pubs.acs.org/doi/pdf/10.1021/acschemneuro.4c00021
- OA Status
- hybrid
- Cited By
- 8
- References
- 91
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4393154963
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4393154963Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1021/acschemneuro.4c00021Digital Object Identifier
- Title
-
Thiophene-Based Ligands for Specific Assignment of Distinct Aβ Pathologies in Alzheimer's DiseaseWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
-
2024-03-25Full publication date if available
- Authors
-
Therése Klingstedt, Linda Lantz, Hamid Shirani, Junyue Ge, Jörg Hanrieder, Rubén Vidal, Bernardino Ghetti, K. Peter R. NilssonList of authors in order
- Landing page
-
https://doi.org/10.1021/acschemneuro.4c00021Publisher landing page
- PDF URL
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https://pubs.acs.org/doi/pdf/10.1021/acschemneuro.4c00021Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
hybridOpen access status per OpenAlex
- OA URL
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https://pubs.acs.org/doi/pdf/10.1021/acschemneuro.4c00021Direct OA link when available
- Concepts
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PSEN1, Ligand (biochemistry), Staining, Senile plaques, Alzheimer's disease, Chemistry, Pathology, Amyloid (mycology), Biology, Molecular biology, Biochemistry, Receptor, Amyloid precursor protein, Disease, MedicineTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
8Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 5, 2024: 3Per-year citation counts (last 5 years)
- References (count)
-
91Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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