Breakdown of specific functional brain networks in clinical variants of Alzheimer's disease: Ageing Research Reviews

L. Pini, A.M. Wennberg, A. Salvalaggio, A. Vallesi, M. Pievani, M. Corbetta

Research output: Contribution to journalArticlepeer-review


Alzheimer's disease (AD) is characterized by different clinical entities. Although AD phenotypes share a common molecular substrate (i.e., amyloid beta and tau accumulation), several clinicopathological differences exist. Brain functional networks might provide a macro-scale scaffolding to explain this heterogeneity. In this review, we summarize the evidence linking different large-scale functional network abnormalities to distinct AD phenotypes. Specifically, executive deficits in early-onset AD link with the dysfunction of networks that support sustained attention and executive functions. Posterior cortical atrophy relates to the breakdown of visual and dorsal attentional circuits, while the primary progressive aphasia variant of AD may be associated with the dysfunction of the left-lateralized language network. Additionally, network abnormalities might provide in vivo signatures for distinguishing proteinopathies that mimic AD, such as TAR DNA binding protein 43 related pathologies. These network differences vis-a-vis clinical syndromes are more evident in the earliest stage of AD. Finally, we discuss how these findings might pave the way for new tailored interventions targeting the most vulnerable brain circuit at the optimal time window to maximize clinical benefits. © 2021 Elsevier B.V.
Original languageEnglish
Article number101482
JournalAgeing Res. Rev.
Publication statusPublished - 2021


  • Alzheimer's disease
  • Early-onset
  • Functional connectivity in atypical AD
  • Language
  • Network-symptoms coupling
  • Posterior cortical atrophy
  • TAR DNA binding protein
  • amyloid beta protein
  • Alzheimer disease
  • attention
  • behavior
  • brain cortex atrophy
  • executive function
  • functional connectivity
  • human
  • language network
  • modulation
  • nerve cell network
  • neuropathology
  • phenotype
  • primary progressive aphasia
  • Review
  • brain
  • diagnostic imaging
  • nuclear magnetic resonance imaging
  • Alzheimer Disease
  • Amyloid beta-Peptides
  • Brain
  • Executive Function
  • Humans
  • Magnetic Resonance Imaging
  • Phenotype


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