Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer's disease
(2021) In Brain : a journal of neurology 144(1). p.310-324- Abstract
It is currently unclear how amyloid-β and tau deposition are linked to changes in synaptic function and axonal structure over the course of Alzheimer's disease. Here, we assessed these relationships by measuring presynaptic (synaptosomal-associated protein 25, SNAP25; growth-associated protein 43, GAP43), postsynaptic (neurogranin, NRGN) and axonal (neurofilament light chain) markers in the CSF of individuals with varying levels of amyloid-β and tau pathology based on 18F-flutemetamol PET and 18F-flortaucipir PET. In addition, we explored the relationships between synaptic and axonal markers with cognition as well as functional and anatomical brain connectivity markers derived from resting-state functional MRI and diffusion tensor... (More)
It is currently unclear how amyloid-β and tau deposition are linked to changes in synaptic function and axonal structure over the course of Alzheimer's disease. Here, we assessed these relationships by measuring presynaptic (synaptosomal-associated protein 25, SNAP25; growth-associated protein 43, GAP43), postsynaptic (neurogranin, NRGN) and axonal (neurofilament light chain) markers in the CSF of individuals with varying levels of amyloid-β and tau pathology based on 18F-flutemetamol PET and 18F-flortaucipir PET. In addition, we explored the relationships between synaptic and axonal markers with cognition as well as functional and anatomical brain connectivity markers derived from resting-state functional MRI and diffusion tensor imaging. We found that the presynaptic and postsynaptic markers SNAP25, GAP43 and NRGN are elevated in early Alzheimer's disease i.e. in amyloid-β-positive individuals without evidence of tau pathology. These markers were associated with greater amyloid-β pathology, worse memory and functional changes in the default mode network. In contrast, neurofilament light chain was abnormal in later disease stages, i.e. in individuals with both amyloid-β and tau pathology, and correlated with more tau and worse global cognition. Altogether, these findings support the hypothesis that amyloid-β and tau might have differential downstream effects on synaptic and axonal function in a stage-dependent manner, with amyloid-related synaptic changes occurring first, followed by tau-related axonal degeneration.
(Less)
- author
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- amyloid-β, MRI, neurofilament, neurogranin, PET, tau PET
- in
- Brain : a journal of neurology
- volume
- 144
- issue
- 1
- pages
- 15 pages
- publisher
- Oxford University Press
- external identifiers
-
- scopus:85102153601
- pmid:33279949
- ISSN
- 1460-2156
- DOI
- 10.1093/brain/awaa395
- language
- English
- LU publication?
- yes
- id
- 4a2e0e0a-2e46-4b91-996c-f3f50242e74b
- date added to LUP
- 2021-03-17 10:55:15
- date last changed
- 2024-04-18 04:37:33
@article{4a2e0e0a-2e46-4b91-996c-f3f50242e74b, abstract = {{<p>It is currently unclear how amyloid-β and tau deposition are linked to changes in synaptic function and axonal structure over the course of Alzheimer's disease. Here, we assessed these relationships by measuring presynaptic (synaptosomal-associated protein 25, SNAP25; growth-associated protein 43, GAP43), postsynaptic (neurogranin, NRGN) and axonal (neurofilament light chain) markers in the CSF of individuals with varying levels of amyloid-β and tau pathology based on 18F-flutemetamol PET and 18F-flortaucipir PET. In addition, we explored the relationships between synaptic and axonal markers with cognition as well as functional and anatomical brain connectivity markers derived from resting-state functional MRI and diffusion tensor imaging. We found that the presynaptic and postsynaptic markers SNAP25, GAP43 and NRGN are elevated in early Alzheimer's disease i.e. in amyloid-β-positive individuals without evidence of tau pathology. These markers were associated with greater amyloid-β pathology, worse memory and functional changes in the default mode network. In contrast, neurofilament light chain was abnormal in later disease stages, i.e. in individuals with both amyloid-β and tau pathology, and correlated with more tau and worse global cognition. Altogether, these findings support the hypothesis that amyloid-β and tau might have differential downstream effects on synaptic and axonal function in a stage-dependent manner, with amyloid-related synaptic changes occurring first, followed by tau-related axonal degeneration.</p>}}, author = {{Pereira, Joana B. and Janelidze, Shorena and Ossenkoppele, Rik and Kvartsberg, Hlin and Brinkmalm, Ann and Mattsson-Carlgren, Niklas and Stomrud, Erik and Smith, Ruben and Zetterberg, Henrik and Blennow, Kaj and Hansson, Oskar}}, issn = {{1460-2156}}, keywords = {{amyloid-β; MRI; neurofilament; neurogranin; PET; tau PET}}, language = {{eng}}, number = {{1}}, pages = {{310--324}}, publisher = {{Oxford University Press}}, series = {{Brain : a journal of neurology}}, title = {{Untangling the association of amyloid-β and tau with synaptic and axonal loss in Alzheimer's disease}}, url = {{http://dx.doi.org/10.1093/brain/awaa395}}, doi = {{10.1093/brain/awaa395}}, volume = {{144}}, year = {{2021}}, }