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. 2023 Nov;19(11):5095-5102.
doi: 10.1002/alz.13103. Epub 2023 Apr 27.

Higher plasma β-synuclein indicates early synaptic degeneration in Alzheimer's disease

Patrick Oeckl  1   2 , Shorena Janelidze  3 , Steffen Halbgebauer  1   2 , Erik Stomrud  3   4 , Sebastian Palmqvist  3   4 , Markus Otto  2   5 , Oskar Hansson  3   4
Affiliations

Higher plasma β-synuclein indicates early synaptic degeneration in Alzheimer's disease

Patrick Oeckl et al. Alzheimers Dement. 2023 Nov.

Abstract

Introduction: β-Synuclein is an emerging synaptic blood biomarker for Alzheimer's disease (AD) but differences in β-synuclein levels in preclinical AD and its association with amyloid and tau pathology have not yet been studied.

Methods: We measured plasma β-synuclein levels in cognitively unimpaired individuals with positive Aβ-PET (i.e., preclinical AD, N = 48) or negative Aβ-PET (N = 61), Aβ-positive patients with mild cognitive impairment (MCI, N = 36), and Aβ-positive AD dementia (N = 85). Amyloid (A) and tau (T) pathology were assessed by [18 F]flutemetamol and [18 F]RO948 PET.

Results: Plasma β-synuclein levels were higher in preclinical AD and even higher in MCI and AD dementia. Stratification according to amyloid/tau pathology revealed higher β-synuclein in A+ T- and A+ T+ subjects compared with A- T- . Plasma β-synuclein levels were related to tau and Aβ pathology and associated with temporal cortical thinning and cognitive impairment.

Discussion: Our data indicate that plasma β-synuclein might track synaptic dysfunction, even during the preclinical stages of AD.

Highlights: Plasma β-synuclein is already higher in preclinical AD. Plasma β-synuclein is higher in MCI and AD dementia than in preclinical AD. Aβ- and tau-PET SUVRs are associated with plasma β-synuclein levels. Plasma β-synuclein is already higher in tau-PET negative subjects. Plasma β-synuclein is related to temporal cortical atrophy and cognitive impairment.

Keywords: amyloid-β PET; blood biomarker; preclinical Alzheimer's disease; synaptic degeneration; tau-PET; β-Synuclein.

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References

REFERENCES

    1. Terry RD, Masliah E, Salmon DP, et al. Physical basis of cognitive alterations in alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30:572-580. doi: 10.1002/ana.410300410
    1. Camporesi E, Nilsson J, Brinkmalm A, et al. Fluid biomarkers for synaptic dysfunction and loss. Biomark Insights. 2020;15:1177271920950319. doi: 10.1177/1177271920950319
    1. Oeckl P, Halbgebauer S, Anderl-Straub S, et al. Targeted mass spectrometry suggests beta-synuclein as synaptic blood marker in Alzheimer's disease. J Proteome Res. 2020;19:1310-1318. doi: 10.1021/acs.jproteome.9b00824
    1. Halbgebauer S, Oeckl P, Steinacker P, et al. Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2021;92:349-356. doi: 10.1136/jnnp-2020-324306
    1. Oeckl P, Metzger F, Nagl M, et al. Alpha-, beta-, and gamma-synuclein quantification in cerebrospinal fluid by multiple reaction monitoring reveals increased concentrations in Alzheimer's and creutzfeldt-jakob disease but no alteration in synucleinopathies. Mol Cell Proteomics. 2016;15:3126-3138. doi: 10.1074/mcp.M116.059915

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