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Nat Commun. 2017 Oct 31;8(1):1214. doi: 10.1038/s41467-017-01150-x.

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

Author information

1
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden. sebastian.palmqvist@med.lu.se.
2
Department of Neurology, Skåne University Hospital, Lund, Sweden. sebastian.palmqvist@med.lu.se.
3
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden.
4
Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
5
Department of Neurology, Skåne University Hospital, Lund, Sweden.
6
Memory Clinic, Skåne University Hospital, Malmö, Sweden.
7
Department of Psychiatry and Neurochemstry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
8
Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
9
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK.
10
Helen Wills Neuroscience Institute, University of California, Berkeley, USA.
11
Clinical Memory Research Unit, Department of Clinical Sciences, Malmö, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.
12
Memory Clinic, Skåne University Hospital, Malmö, Sweden. oskar.hansson@med.lu.se.

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 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.

PMID:
29089479
PMCID:
PMC5663717
DOI:
10.1038/s41467-017-01150-x
[Indexed for MEDLINE]
Free PMC Article

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