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

Coomans, Emma M. (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
Schoonhoven, Deborah N. (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
Tuncel, Hayel (author)
Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam
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Verfaillie, Sander C.J. (author)
Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam
Wolters, Emma E. (author)
Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam
Boellaard, Ronald (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
Ossenkoppele, Rik (author)
Lund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
den Braber, Anouk (author)
Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam
Scheper, Wiep (author)
Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam
Schober, Patrick (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
Sweeney, Steven P. (author)
Rodin Therapeutics Inc.
Ryan, J. Michael (author)
Rodin Therapeutics Inc.
Schuit, Robert C. (author)
Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam
Windhorst, Albert D. (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
Barkhof, Frederik (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam,University College London
Scheltens, Philip (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
Golla, Sandeep S.V. (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
Hillebrand, Arjan (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
Gouw, Alida A. (author)
Vrije Universiteit Amsterdam,Amsterdam UMC - Vrije Universiteit Amsterdam
van Berckel, Bart N.M. (author)
Amsterdam UMC - Vrije Universiteit Amsterdam,Vrije Universiteit Amsterdam
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 (creator_code:org_t)
2021-02-05
2021
English.
In: Alzheimer's Research and Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 13:1
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Keyword

Alzheimer
MEG
PET
Synaptic density
Synaptic function
Tau

Publication and Content Type

art (subject category)
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