Novel targets in Alzheimer's disease: A special focus on microglia

Research output: Contribution to journalReview articlepeer-review


Several years after the intriguing novelty in the β-amyloid (Aβ) cascade hypothesis, where the Aβ oligomers emerged as the most detrimental species in the neuropathogenic process of Alzheimer's disease (AD) in place of fibrillar plaques, more recently innate immune system have come on stage as the other prominent factor. Neuroinflammation apparently contributes to AD eziopathogenesis, in large part through overactivation of microglia cells. Genetic and experimental studies strongly support the contribution of the immune system to increasing the risk of AD and participating in its progression. Besides the central immune response mediated by resident microglial cells, peripheral immune challenges may have profound negative effects on brain physiology as well, such as those originating from the gut microbiota. Despite the initial immune response to defend the organism, perpetuation seemingly turns into a chronic detrimental phenomenon that contributes to neuronal dysfunction and exacerbation of the disease. Several new immune-druggable targets are now under investigation, but much still remains to be defined about their precise role and whether and how their physiological activity changes in the injurious context of AD. From a therapeutic perspective, we can undoubtedly consider that AD is no longer solely an Aβ pathology, but rather a multifaceted disorder calling for multi-target therapies. New therapies fighting AD must still counteract Aβ but must also restore appropriate immune defences by tempering maladaptive factors and enabling beneficial responses.

Original languageEnglish
Pages (from-to)402-413
Number of pages12
JournalPharmacological Research
Publication statusPublished - Apr 2018


  • Alzheimer Disease/microbiology
  • Animals
  • Gastrointestinal Microbiome
  • Humans
  • Inflammation
  • Microglia


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