Alzheimer's Disease May Start Early Due to Unbalanced Gut Bacteria

Jenn Hoskins
11th September, 2024

Alzheimer's Disease May Start Early Due to Unbalanced Gut Bacteria

Image Source: Natural Science News, 2024

Key Findings

  • Researchers at the Nathan Kline Institute found that early-life disruptions in the gut microbiome might trigger Alzheimer's disease (AD) pathology
  • The study suggests that antibiotic exposure in early life could worsen AD-like symptoms by affecting the gut microbiome
  • The researchers propose that specific microbiological interventions might mitigate the progression of AD, offering new therapeutic strategies
Alzheimer's disease (AD) is a debilitating neurodegenerative disorder with few effective treatment options. Researchers at the Nathan Kline Institute have been investigating innovative approaches for prevention and treatment, focusing on the human microbiome—the vast consortium of microorganisms that inhabit our bodies[1]. The microbiome plays significant roles in immune function, metabolism, and cognitive development, and may also be involved in neurodegeneration. AD and Alzheimer's disease-related dementias (ADRD) are complex conditions that begin before clinical symptoms appear. Despite extensive research, the triggers initiating AD/ADRD remain undefined. The Nathan Kline Institute's study posits that disruptions in the gut microbiome during early life could initiate a pathological cascade affecting brain circuits, particularly those in the septohippocampal and cortical regions. Previous research has shown that the hallmark pathological features of AD—amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau—are present before the onset of dementia and throughout its progression[2]. Cognitive decline in AD correlates more strongly with synaptic loss than with Aβ plaques or NFTs alone. This suggests that a multifaceted approach, incorporating various molecular, cellular, and imaging markers, is essential for understanding the transition from normal cognitive function to mild cognitive impairment (MCI) and full-blown AD[2]. The Nathan Kline Institute researchers hypothesize that antibiotic exposure in early life could exacerbate AD-like symptoms. This hypothesis aligns with findings that dysregulation of the gut microbiome is associated with dementia[3]. For instance, higher concentrations of faecal ammonia have been linked to an increased risk of dementia, while higher levels of faecal lactic acid appear to be protective[3]. These findings suggest that the gut microbiome and its metabolites could play a crucial role in the development and progression of AD. The study proposes to use established AD/ADRD models to investigate how changes in early-life microbiota might lead to hallmark AD pathology. This approach could reveal whether specific microbiological interventions might mitigate the disease's progression. The researchers plan to use various models to test their hypotheses, potentially leading to new therapeutic strategies. Understanding the microbiome's role in AD could also provide insights into broader questions about the human microbiome's impact on health and disease. Previous studies have shown that the microbiome is linked to conditions such as obesity, inflammatory bowel disease, arthritis, and autism[4]. Improvements in DNA sequencing and other technologies have enhanced our ability to study these microbial communities, but many challenges remain[4]. The Nathan Kline Institute's research aims to move from correlational studies to causal understanding, ultimately translating findings into therapies. The hypothesis that the human microbiome evolved mechanisms that influence the mortality of senescent individuals also adds an evolutionary perspective to this research[5]. Early human populations may have benefited from microbes that contributed to the demise of older individuals, thereby maintaining population stability. However, these mechanisms could now be contributing to modern degenerative diseases like AD, as the extended longevity of contemporary humans is a recent societal development[5]. In summary, the Nathan Kline Institute's study aims to explore how early-life disruptions in the gut microbiome might trigger AD pathology. By using established models and focusing on the microbiome's role, the researchers hope to uncover new avenues for prevention and treatment. This research builds on existing knowledge about the microbiome's impact on health and disease, offering a promising new direction in the fight against Alzheimer's disease.

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References

Main Study

1) Alzheimer's Disease Has Its Origins in Early Life via a Perturbed Microbiome.

Published 10th September, 2024

https://doi.org/10.1093/infdis/jiae200

Related Studies

2) Molecular and cellular pathophysiology of preclinical Alzheimer's disease.

https://doi.org/10.1016/j.bbr.2016.05.030

3) Relationship between dementia and gut microbiome-associated metabolites: a cross-sectional study in Japan.

https://doi.org/10.1038/s41598-020-65196-6

4) Current understanding of the human microbiome.

https://doi.org/10.1038/nm.4517

5) Host demise as a beneficial function of indigenous microbiota in human hosts.

https://doi.org/10.1128/mBio.02262-14


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