Untangling the roles of amyloid and tau in synaptic and axonal loss in the course of Alzheimer’s disease
Year: 2020
Type: article
Study design: Observational Study
Abstract: Background It is currently unclear how rising amyloid‐β (Aβ) and tau tangles are linked to changes in synaptic function and axonal structure over the course of Alzheimer’s disease (AD). Method Here we assess how presynaptic (synaptosomal‐associated protein 25, SNAP‐25), postsynaptic (neurogranin, Ng) and axonal (neurofilament light chain, NfL) biomarkers change in early and late AD, in individuals with or without Aβ and tau pathology based on Aβ‐PET (18F‐flutemetamol) and tau‐PET (18F‐flortaucipir). In addition, we explore the relationship between these biomarkers with memory and global cognition as well as functional and anatomical brain connectivity. Result Our findings show that the synaptic markers SNAP‐25 and Ng are increased in early AD, i.e. in Aβ‐positive individuals without evidence of tau pathology. In this group, higher synaptic levels were associated with more Aβ pathology, worse memory and functional changes in the default‐mode network, but not global cognition or anatomical connectivity. In contrast, NfL levels became abnormal in later disease stages, i.e. in individuals with both Aβ and tau pathology. In this group, higher NfL was associated with more tau and worse global cognition, but not Aβ pathology or default mode network connectivity. Finally, reduced anatomical connectivity was only associated with tau pathology in late AD. Conclusion Altogether, these findings support the hypothesis that Aβ and tau have downstream effects on synaptic and axonal function in a stage‐dependent manner. Increases in Aβ are related to presynaptic and postsynaptic markers, which affect functional connectivity in early disease stages. This is followed by an increase of tau, which affects both axonal markers and anatomical connectivity in later disease stages.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.043169
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3113178231