Alzheimer's Disease: A Systems View Provides a Unifying Explanation of Its Development

Corlia Grobler, Marvi van Tongeren, Jan Gettemans, Douglas B. Kell, Etheresia Pretorius

Research output: Contribution to journalReviewpeer-review


Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting 50 million people globally. It is characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles, consisting of amyloid-β and hyperphosphorylated tau proteins, respectively. Despite global research efforts, there is currently no cure available, due in part to an incomplete understanding of the disease pathogenesis. Numerous possible mechanisms, or hypotheses, explaining the origins of sporadic or late-onset AD have been proposed, including the amyloid-β, inflammatory, vascular, and infectious hypotheses. However, despite ample evidence, the failure of multiple trial drugs at the clinical stage illuminates the possible pitfalls of these hypotheses. Systems biology is a strategy which aims to elucidate the interactions between parts of a whole. Using this approach, the current paper shows how the four previously mentioned hypotheses of AD pathogenesis can be intricately connected. This approach allows for seemingly contradictory evidence to be unified in a system-focused explanation of sporadic AD development. Within this view, it is seen that infectious agents, such as P. gingivalis, may play a central role. The data presented here shows that when present, P. gingivalis or its virulence factors, such as gingipains, may induce or exacerbate pathologies underlying sporadic AD. This evidence supports the view that infectious agents, and specifically P. gingivalis, may be suitable treatment targets in AD.

Original languageEnglish
JournalJournal of Alzheimer's Disease
Issue number1
Pages (from-to)43-70
Number of pages28
Publication statusPublished - 2023


  • Alzheimer’s disease
  • infectious agents
  • systemic inflammation
  • systems biology


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