BioMed Central recognizes the best scientific research published across its Open Access journals through the annual BioMed Central Research Awards, covering ten different categories. In the category of Neuroscience, Neurology and Psychiatry, Irene Knuesel from the University of Zurich, Switzerland won for her article ‘Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice’ published in the Journal of Neuroinflammation.

“To win the Neuroscience, Neurology and Psychiatry Award has been a great honour and the best motivation to continue our research devoted to a better understanding of late-onset Alzheimer’s disease pathophysiology,” said Knuesel.

Alzheimer’s disease (AD) is the most common cause of age-related dementia, with a majority of cases having a sporadic, rather than familial, origin. Research suggests neuroinflammation of the brain is linked to the pathogenesis of the disease, however previous studies had not established whether this link was causal.

Kneusel and colleagues set out to investigate this association in a novel mouse model for sporadic AD using polyriboinosinic-polyribocytidilic acid (PolyI:C), a viral mimic that stimulates the immune system.

 

“It seems likely that chronic inflammation due to infection could be an early event in the development of AD.”
Irene Knuesel, University of Zurich

 

Based on the similarity between the changes in the immune-challenged mice and the development of AD in humans, this comprehensive study suggests that systemic infections represent a major risk factor for the development of AD. Knuesel and colleagues notably provide the first evidence that a pre-natal systemic immune challenge in mice results in chronic inflammation, increased levels of amyloid precursor protein, tau mislocalisation and cognitive impairments, all of which leave the brain vulnerable to pathological aging and AD. Moreover, a subsequent systemic immune challenge in adulthood further exacerbates the situation leading to neuropathological hallmarks representative of a precursor stage of early AD.

Guojun Bu, professor of neuroscience at the Mayo Clinic, USA and co-Editor-in-Chief of Molecular Neurodegeneration, was one of three judges for the Research Awards in this category, and commended the studies novel observation of “the close relationship between the immune system and the pathogenic process of AD.”

These findings provide compelling evidence for the causative role of systemic immune challenges in the development of AD-like neuropathology and also provides the scientific community with a unique tool, in the PolyI:C mouse model, to investigate the molecular mechanisms underlying early pathophysiological changes in sporadic AD. Knuesel continues to investigate neuroinflammation in AD, specifically with aim of identifying the molecular link between neuroinflammation-induced alterations in the processing of amyloid precursor protein and the hyperphosphorylation of tau.

“The relationship of inflammatory processes and neurodegeneration is frequently discussed but has not been seriously examined in animal models so far”, noted Research Award judge Amos Korczyn from the department of neurology at Tel Aviv University, Israel. “This study is very comprehensive, including both biochemical and anatomical changes in a systematic study of wild-type and transgenic animals. The work is outstanding and I expect it to be of high impact.”

 

More about the researcher(s)

  • Irene Knuesel, senior research scientist, Institute of Pharmacology and Toxicology, University of Zurich, Switzerland.

    Irene Knuesel

    Irene Knuesel received her PhD in Molecular Neuroscience from the University of Zurich, Switzerland. Awarded with a fellowship from the Swiss National Science Foundation, she carried out her postdoctoral training in the laboratory of Mary Kennedy at the California Institute of Technology, USA. Following a junior group leader position with Joram Feldon at the Technical… Read more »

Research

Highly AccessedOpen Access

Systemic immune challenges trigger and drive Alzheimer-like neuropathology in mice

Krstic D, Madhusudan A, Doehner J, Vogel P, Notter T, Imhof C, Manalastas A, Hilfiker M et al.

Journal of Neuroinflammation 2012, 9:151


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