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In vivo tau pathology is associated with synaptic loss and altered synaptic function

Coomans, Emma M. ; Schoonhoven, Deborah N. ; Tuncel, Hayel ; Verfaillie, Sander C.J. ; Wolters, Emma E. ; Boellaard, Ronald ; Ossenkoppele, Rik LU ; den Braber, Anouk ; Scheper, Wiep and Schober, Patrick , et al. (2021) In Alzheimer's Research and Therapy 13(1).
Abstract

Background: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. Methods: Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [18F]flortaucipir PET, dynamic 60-min [11C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [18F]flortaucipir-... (More)

Background: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([18F]flortaucipir PET), synaptic density (synaptic vesicle 2A [11C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. Methods: Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [18F]flortaucipir PET, dynamic 60-min [11C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [18F]flortaucipir- and [11C]UCB-J-specific binding (binding potential, BPND) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [18F]flortaucipir BPND, [11C]UCB-J BPND and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. Results: Across subjects, higher regional [18F]flortaucipir uptake was associated with lower [11C]UCB-J uptake. Within subjects, the association between [11C]UCB-J and [18F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [18F]flortaucipir and lower [11C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. Conclusions: These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer, MEG, PET, Synaptic density, Synaptic function, Tau
in
Alzheimer's Research and Therapy
volume
13
issue
1
article number
35
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85100547302
  • pmid:33546722
ISSN
1758-9193
DOI
10.1186/s13195-021-00772-0
language
English
LU publication?
yes
id
723ad8a2-259b-4a94-8ec7-d408526d420f
date added to LUP
2021-02-22 08:59:25
date last changed
2021-06-08 05:37:00
@article{723ad8a2-259b-4a94-8ec7-d408526d420f,
  abstract     = {<p>Background: The mechanism of synaptic loss in Alzheimer’s disease is poorly understood and may be associated with tau pathology. In this combined positron emission tomography (PET) and magnetoencephalography (MEG) study, we aimed to investigate spatial associations between regional tau pathology ([<sup>18</sup>F]flortaucipir PET), synaptic density (synaptic vesicle 2A [<sup>11</sup>C]UCB-J PET) and synaptic function (MEG) in Alzheimer’s disease. Methods: Seven amyloid-positive Alzheimer’s disease subjects from the Amsterdam Dementia Cohort underwent dynamic 130-min [<sup>18</sup>F]flortaucipir PET, dynamic 60-min [<sup>11</sup>C]UCB-J PET with arterial sampling and 2 × 5-min resting-state MEG measurement. [<sup>18</sup>F]flortaucipir- and [<sup>11</sup>C]UCB-J-specific binding (binding potential, BP<sub>ND</sub>) and MEG spectral measures (relative delta, theta and alpha power; broadband power; and peak frequency) were assessed in cortical brain regions of interest. Associations between regional [<sup>18</sup>F]flortaucipir BP<sub>ND</sub>, [<sup>11</sup>C]UCB-J BP<sub>ND</sub> and MEG spectral measures were assessed using Spearman correlations and generalized estimating equation models. Results: Across subjects, higher regional [<sup>18</sup>F]flortaucipir uptake was associated with lower [<sup>11</sup>C]UCB-J uptake. Within subjects, the association between [<sup>11</sup>C]UCB-J and [<sup>18</sup>F]flortaucipir depended on within-subject neocortical tau load; negative associations were observed when neocortical tau load was high, gradually changing into opposite patterns with decreasing neocortical tau burden. Both higher [<sup>18</sup>F]flortaucipir and lower [<sup>11</sup>C]UCB-J uptake were associated with altered synaptic function, indicative of slowing of oscillatory activity, most pronounced in the occipital lobe. Conclusions: These results indicate that in Alzheimer’s disease, tau pathology is closely associated with reduced synaptic density and synaptic dysfunction.</p>},
  author       = {Coomans, Emma M. and Schoonhoven, Deborah N. and Tuncel, Hayel and Verfaillie, Sander C.J. and Wolters, Emma E. and Boellaard, Ronald and Ossenkoppele, Rik and den Braber, Anouk and Scheper, Wiep and Schober, Patrick and Sweeney, Steven P. and Ryan, J. Michael and Schuit, Robert C. and Windhorst, Albert D. and Barkhof, Frederik and Scheltens, Philip and Golla, Sandeep S.V. and Hillebrand, Arjan and Gouw, Alida A. and van Berckel, Bart N.M.},
  issn         = {1758-9193},
  language     = {eng},
  number       = {1},
  publisher    = {BioMed Central (BMC)},
  series       = {Alzheimer's Research and Therapy},
  title        = {In vivo tau pathology is associated with synaptic loss and altered synaptic function},
  url          = {http://dx.doi.org/10.1186/s13195-021-00772-0},
  doi          = {10.1186/s13195-021-00772-0},
  volume       = {13},
  year         = {2021},
}