Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Dec 31;14(1):201.
doi: 10.1186/s13195-022-01150-0.

Alpha-synuclein: a pathological factor with Aβ and tau and biomarker in Alzheimer's disease

Kyu Hwan Shim #  1 , Min Ju Kang #  2 , Young Chul Youn  3 , Seong Soo A An  4 , SangYun Kim  5
Affiliations
Review

Alpha-synuclein: a pathological factor with Aβ and tau and biomarker in Alzheimer's disease

Kyu Hwan Shim et al. Alzheimers Res Ther. .

Abstract

Background: Alpha-synuclein (α-syn) is considered the main pathophysiological protein component of Lewy bodies in synucleinopathies. α-Syn is an intrinsically disordered protein (IDP), and several types of structural conformations have been reported, depending on environmental factors. Since IDPs may have distinctive functions depending on their structures, α-syn can play different roles and interact with several proteins, including amyloid-beta (Aβ) and tau, in Alzheimer's disease (AD) and other neurodegenerative disorders.

Main body: In previous studies, α-syn aggregates in AD brains suggested a close relationship between AD and α-syn. In addition, α-syn directly interacts with Aβ and tau, promoting mutual aggregation and exacerbating the cognitive decline. The interaction of α-syn with Aβ and tau presented different consequences depending on the structural forms of the proteins. In AD, α-syn and tau levels in CSF were both elevated and revealed a high positive correlation. Especially, the CSF α-syn concentration was significantly elevated in the early stages of AD. Therefore, it could be a diagnostic marker of AD and help distinguish AD from other neurodegenerative disorders by incorporating other biomarkers.

Conclusion: The overall physiological and pathophysiological functions, structures, and genetics of α-syn in AD are reviewed and summarized. The numerous associations of α-syn with Aβ and tau suggested the significance of α-syn, as a partner of the pathophysiological roles in AD. Understanding the involvements of α-syn in the pathology of Aβ and tau could help address the unresolved issues of AD. In particular, the current status of the CSF α-syn in AD recommends it as an additional biomarker in the panel for AD diagnosis.

Keywords: Alzheimer’s disease; Amyloid-beta; Biomarker; Cerebrospinal fluid; Tau; α-Synuclein.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Characteristics of the three regions in α-synuclein. α-syn, alpha-synuclein; NAC, non-amyloid-beta component
Fig. 2
Fig. 2
Conformational diversity of α-syn. Modeling of α-synuclein monomer (PDB: 1XQ8), tetramer, and fibril from cryo-electron microscopy for both the twister (PDB: 6CU8) and rod polymorph (PDB: 6CU7). α-syn, alpha-synuclein; cryo-EM, cryo-electron microscopy
Fig. 3
Fig. 3
Schematic diagram of the possible relationship of α-synuclein with amyloid-beta, tau, and tubulin α-syn, alpha-synuclein; Aβ, amyloid-beta
Fig. 4
Fig. 4
Meta-analysis of the cerebrospinal fluid α-synuclein level in Alzheimer’s disease and healthy controls CSF, cerebrospinal fluid; α-syn, alpha-synuclein; AD, Alzheimer’s disease; HC, healthy controls
See this image and copyright information in PMC

References

    1. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature. 1997;388(6645):839–840. doi: 10.1038/42166. - DOI - PubMed
    1. Kim WS, Kågedal K, Halliday GM. Alpha-synuclein biology in Lewy body diseases. Alzheimer’s Research & Therapy. 2014;6(5):73. - PMC - PubMed
    1. Ueda K, Fukushima H, Masliah E, Xia Y, Iwai A, Yoshimoto M, et al. Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease. Proc Natl Acad Sci U S A. 1993;90(23):11282–11286. doi: 10.1073/pnas.90.23.11282. - DOI - PMC - PubMed
    1. Masliah E, Iwai A, Mallory M, Ueda K, Saitoh T. Altered presynaptic protein NACP is associated with plaque formation and neurodegeneration in Alzheimer’s disease. Am J Pathol. 1996;148(1):201–210. - PMC - PubMed
    1. Arai Y, Yamazaki M, Mori O, Muramatsu H, Asano G, Katayama Y. Alpha-synuclein-positive structures in cases with sporadic Alzheimer’s disease: morphology and its relationship to tau aggregation. Brain Res. 2001;888(2):287–296. doi: 10.1016/S0006-8993(00)03082-1. - DOI - PubMed

Publication types