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

Oeckl, Patrick ; Janelidze, Shorena LU ; Halbgebauer, Steffen ; Stomrud, Erik LU orcid ; Palmqvist, Sebastian LU orcid ; Otto, Markus and Hansson, Oskar LU orcid (2023) In Alzheimer's and Dementia 19(11). p.5095-5102
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 [18F]flutemetamol and [18F]RO948 PET. RESULTS: Plasma β-synuclein levels were higher in preclinical AD and even higher in MCI and AD dementia. Stratification according to... (More)

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 [18F]flutemetamol and [18F]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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amyloid-β PET, blood biomarker, preclinical Alzheimer's disease, synaptic degeneration, tau-PET, β-Synuclein
in
Alzheimer's and Dementia
volume
19
issue
11
pages
5095 - 5102
publisher
Wiley
external identifiers
  • pmid:37186338
  • scopus:85157976962
ISSN
1552-5260
DOI
10.1002/alz.13103
language
English
LU publication?
yes
id
68b6fdc6-92be-45e4-b5d6-34cc36f69270
date added to LUP
2023-08-16 12:36:24
date last changed
2024-04-20 00:44:25
@article{68b6fdc6-92be-45e4-b5d6-34cc36f69270,
  abstract     = {{<p>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 [<sup>18</sup>F]flutemetamol and [<sup>18</sup>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<sup>+</sup>T<sup>−</sup> and A<sup>+</sup>T<sup>+</sup> subjects compared with A<sup>−</sup>T<sup>−</sup>. 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.</p>}},
  author       = {{Oeckl, Patrick and Janelidze, Shorena and Halbgebauer, Steffen and Stomrud, Erik and Palmqvist, Sebastian and Otto, Markus and Hansson, Oskar}},
  issn         = {{1552-5260}},
  keywords     = {{amyloid-β PET; blood biomarker; preclinical Alzheimer's disease; synaptic degeneration; tau-PET; β-Synuclein}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{5095--5102}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Higher plasma β-synuclein indicates early synaptic degeneration in Alzheimer's disease}},
  url          = {{http://dx.doi.org/10.1002/alz.13103}},
  doi          = {{10.1002/alz.13103}},
  volume       = {{19}},
  year         = {{2023}},
}