Breakdown of specific functional brain networks in clinical variants of Alzheimer's disease

Lorenzo Pini, Alexandra M. Wennberg, Alessandro Salvalaggio, Antonino Vallesi, Michela Pievani, Maurizio Corbetta

Research output: Contribution to journalReview articlepeer-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.

Original languageEnglish
Article number101482
JournalAgeing Research Reviews
Publication statusPublished - Dec 2021


  • Alzheimer's disease
  • Early-onset
  • Functional connectivity in atypical AD
  • Language
  • Network-symptoms coupling
  • Posterior cortical atrophy

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Ageing
  • Molecular Biology
  • Neurology


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