Higher plasma β-synuclein indicates early synaptic degeneration in Alzheimer's disease
(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.
(Less)
- author
- Oeckl, Patrick ; Janelidze, Shorena LU ; Halbgebauer, Steffen ; Stomrud, Erik LU ; Palmqvist, Sebastian LU ; Otto, Markus and Hansson, Oskar LU
- organization
- publishing date
- 2023
- 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
-
- scopus:85157976962
- pmid:37186338
- 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
- 2024-10-05 17:50:07
@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}}, }