Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity
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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.
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The record
- Venue
- Nature Communications
- Topic
- Functional Brain Connectivity Studies
- Field
- Neuroscience
- Canadian institutions
- —
- Funders
- National Institute on AgingCanadian Institutes of Health ResearchNational Institutes of HealthIXICOH. Lundbeck A/SKnut och Alice Wallenbergs StiftelseServierSkånes universitetssjukhusVetenskapsrådetMarcus FoundationEisaiLunds UniversitetRoyal Swedish Academy of SciencesNorthern California Institute for Research and EducationGenentechMarcus och Amalia Wallenbergs minnesfondEli Lilly and CompanyU.S. Department of DefenseMeso Scale DiagnosticsAustralian GovernmentF. Hoffmann-La RocheUniversity of Southern CaliforniaPfizerBiogenBioClinicaTorsten Söderbergs StiftelseNovartis Pharmaceuticals CorporationBristol-Myers SquibbFoundation for the National Institutes of Health
- Keywords
- Default mode networkNeuroscienceAmyloid βAmyloid (mycology)Computer scienceFunctional connectivityBusinessBiologyMedicineDiseasePathology
- Has abstract in OpenAlex
- yes