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Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity

Palmqvist, Sebastian LU ; Schöll, Michael LU ; Strandberg, Olof LU ; Mattsson, Niklas LU ; Stomrud, Erik LU ; Zetterberg, Henrik LU ; Blennow, Kaj LU ; Landau, Susan; Jagust, William and Hansson, Oskar LU (2017) In Nature Communications 8(1).
Abstract

It is not known exactly where amyloid-β (Aβ) fibrils begin to accumulate in individuals with Alzheimer's disease (AD). Recently, we showed that abnormal levels of Aβ42 in cerebrospinal fluid (CSF) can be detected before abnormal amyloid can be detected using PET in individuals with preclinical AD. Using these approaches, here we identify the earliest preclinical AD stage in subjects from the ADNI and BioFINDER cohorts. We show that Aβ accumulation preferentially starts in the precuneus, medial orbitofrontal, and posterior cingulate cortices, i.e., several of the core regions of the default mode network (DMN). This early pattern of Aβ accumulation is already evident in individuals with normal Aβ42 in the CSF and normal amyloid PET who... (More)

It is not known exactly where amyloid-β (Aβ) fibrils begin to accumulate in individuals with Alzheimer's disease (AD). Recently, we showed that abnormal levels of Aβ42 in cerebrospinal fluid (CSF) can be detected before abnormal amyloid can be detected using PET in individuals with preclinical AD. Using these approaches, here we identify the earliest preclinical AD stage in subjects from the ADNI and BioFINDER cohorts. We show that Aβ accumulation preferentially starts in the precuneus, medial orbitofrontal, and posterior cingulate cortices, i.e., several of the core regions of the default mode network (DMN). This early pattern of Aβ accumulation is already evident in individuals with normal Aβ42 in the CSF and normal amyloid PET who subsequently convert to having abnormal CSF Aβ42. The earliest Aβ accumulation is further associated with hypoconnectivity within the DMN and between the DMN and the frontoparietal network, but not with brain atrophy or glucose hypometabolism. Our results suggest that Aβ fibrils start to accumulate predominantly within certain parts of the DMN in preclinical AD and already then affect brain connectivity.

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organization
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publication status
published
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in
Nature Communications
volume
8
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85032661576
ISSN
2041-1723
DOI
10.1038/s41467-017-01150-x
language
English
LU publication?
yes
id
ddc8ec37-9149-4eb4-a74e-fe1056f24f3e
date added to LUP
2017-11-14 12:17:33
date last changed
2018-01-07 12:25:49
@article{ddc8ec37-9149-4eb4-a74e-fe1056f24f3e,
  abstract     = {<p>It is not known exactly where amyloid-β (Aβ) fibrils begin to accumulate in individuals with Alzheimer's disease (AD). Recently, we showed that abnormal levels of Aβ42 in cerebrospinal fluid (CSF) can be detected before abnormal amyloid can be detected using PET in individuals with preclinical AD. Using these approaches, here we identify the earliest preclinical AD stage in subjects from the ADNI and BioFINDER cohorts. We show that Aβ accumulation preferentially starts in the precuneus, medial orbitofrontal, and posterior cingulate cortices, i.e., several of the core regions of the default mode network (DMN). This early pattern of Aβ accumulation is already evident in individuals with normal Aβ42 in the CSF and normal amyloid PET who subsequently convert to having abnormal CSF Aβ42. The earliest Aβ accumulation is further associated with hypoconnectivity within the DMN and between the DMN and the frontoparietal network, but not with brain atrophy or glucose hypometabolism. Our results suggest that Aβ fibrils start to accumulate predominantly within certain parts of the DMN in preclinical AD and already then affect brain connectivity.</p>},
  articleno    = {1214},
  author       = {Palmqvist, Sebastian and Schöll, Michael and Strandberg, Olof and Mattsson, Niklas and Stomrud, Erik and Zetterberg, Henrik and Blennow, Kaj and Landau, Susan and Jagust, William and Hansson, Oskar},
  issn         = {2041-1723},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity},
  url          = {http://dx.doi.org/10.1038/s41467-017-01150-x},
  volume       = {8},
  year         = {2017},
}