Emerging roles of N- and C-terminally truncated Aβ species in Alzheimer’s disease
Open accessAbstract
Introduction : Alzheimer's disease (AD) is characterized by a cerebral accumulation and aggregation of amyloid-β (Aβ) peptides, which mainly accumulate in the form of extracellular deposits. In addition to the well-described full-length peptides Aβ 1-40 and Aβ 1-42 , a variety of amino- and carboxy-terminally truncated Aβ variants have been identified in brain samples from sporadic and familial AD cases. Areas covered : This review gives an overview on the role of truncated Aβ species in human AD, as well as in transgenic AD mouse models. We outline the relevance of the most abundant N- and C-truncated Aβ species, highlight potential mechanisms with regard to their generation and discuss their suitability as targets for pharmacological interventions. Expert opinion : A variety of recent clinical trials aiming either at a reduced Aβ production by the use of secretase inhibitors or at increased Aβ clearance by the use of immunotherapy were terminated unsuccessfully. Truncated or post-translationally modified Aβ peptides are becoming increasingly recognized as important players in the etiology of AD and a more thorough comprehension of their cellular origin and biochemical peculiarities might break new ground for therapeutic strategies.
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Aβ4-42 is among the most abundant N-terminally truncated Aβ peptides.
“Among the different Aβ variants, the N-terminally truncated peptide Aβ4–42 is among the most abundant.”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [23]
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Self-citationCharacterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau
Zampar, S., & Wirths, O. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105191 · Cited by 18 · see citing works
“Aβ4–42 peptides are among the first Aβ peptides that have been identified in human AD brain and represent a highly abundant peptide species [1,22,23].”
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- Authors
- Wirths, O., & Zampar, S.
- Affiliations
- Universitätsmedizin Göttingen (DE)
- Corresponding author
- Wirths, Oliver
- Venue
- Expert Opinion on Therapeutic Targets
- Publisher
- Informa UK Limited
- Published
- 2019-12-02
- Volume
- 23
- Issue
- 12
- Pages
- 991-1004
- ISSN
- 1472-8222 (ISSN-L)
- 1744-7631
- OpenAlex
- W2991919636
- Cited by
- 44
- References
- 24
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 7 · 2021: 10 · 2020: 12
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Expert Opinion on Therapeutic Targets (publishedVersion)
- PubMed (publishedVersion)
- GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta, N-terminal truncation, C-terminal truncation, amyloid-beta aggregation, transgenic mouse model, secretase inhibitors, immunotherapy, post-translational modification, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Humans, Immunotherapy, Mice, Transgenic, Amyloid beta-Peptides, Mice
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