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Do microbes play a role in Alzheimer's disease?

ABSTRACT: Alzheimer's disease is a complex and progressive condition that affects essential neurological functions such as memory and reasoning. In the brain, neuronal loss, synaptic dysfunction, proteinopathy, neurofibrillary tangles, and neuroinflammation are the hallmarks of Alzheimer's disease pathophysiology. In addition, recent evidence has highlighted that microbes, whether commensal or pathogenic, also have the ability to interact with their host and to regulate its immune system, therefore participating in the exchanges that lead to peripheral inflammation and neuropathology. Because of this intimate relationship, bacteria, viruses, fungi, and protozoa have been implicated in the development of Alzheimer's disease. Here, we bring together current and most recent evidence of the role of microbes in Alzheimer's disease, raising burning questions that need to be addressed to guide therapeutic approaches and potential prophylactic strategies.

SUBMITTER: Williams ZAP

PROVIDER: S-EPMC11003713 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Do microbes play a role in Alzheimer's disease?

Williams Zoë A P ZAP Lang Leonie L Nicolas Sarah S Clarke Gerard G Cryan John J Vauzour David D Nolan Yvonne M YM

Microbial biotechnology 20240401 4

Alzheimer's disease is a complex and progressive condition that affects essential neurological functions such as memory and reasoning. In the brain, neuronal loss, synaptic dysfunction, proteinopathy, neurofibrillary tangles, and neuroinflammation are the hallmarks of Alzheimer's disease pathophysiology. In addition, recent evidence has highlighted that microbes, whether commensal or pathogenic, also have the ability to interact with their host and to regulate its immune system, therefore partic ...[more]

PMID: 38593310

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Project description:Apple replant disease (ARD) is a severe problem in apple production worldwide. It is caused by a complex of soil biota, leading to small discolorated roots, as well as increased biosynthesis of phytoalexins, total phenolic compounds and antioxidants. We sampled soil from randomized field plots with either apple trees affected by ARD, which were five times replanted every second year, or with healthy trees growing in plots, which had a grass cover during this period. We investigated the contribution of nematodes to ARD by dissecting the soil biota from plots infested with ARD and non-infested control plots into a nematode and a microbe fraction. Nematode communities significantly differed between ARD and control soil as revealed by high-throughput sequencing of 18S rRNA genes. Plant-parasitic nematodes were too low in abundance to explain root damage, and did not significantly differ between ARD and control soil. Their separate and synergistic effect on ARD symptoms of susceptible M26 apple rootstocks was analyzed 4 and 8 weeks after inoculation in three greenhouse experiments. Inoculants were either nematodes from ARD plots (NARD), NARD plus microbes from ARD plots (MARD), NARD plus microbes from control plots (MCon), nematodes from control plots NCon plus MARD, NCon plus MCon, MARD, or MCon, or non-inoculated control. In all three experiments, the combination NARD plus MARD had the strongest adverse effect on the plants, with respect to growth parameters of shoots and roots, total phenolic compounds and phytoalexins in roots, and antioxidants in leaves. NARD also induced ARD but less than NARD plus MARD. NARD plus MCon had delayed effects on the plants compared to NARD plus MARD, suggesting that detrimental nematode-microbe interactions built up with time. Effects of MARD or NCon plus MARD were minor or not distinguishable from those of MCon or non-inoculated control. Overall, the source of the inoculated nematodes -ARD or control soil- and the interaction between ARD nematodes and microbes were highly significant factors determining ARD. In conclusion, exploring the associations of nematodes and microbes in ARD soils will give the chance to unravel the etiology of ARD.

Project description:BackgroundSystemic activation of the immune system can exert detrimental effects on the central nervous system. Periodontitis, a chronic disease of the oral cavity, is a common source of systemic inflammation. Neuroinflammation might be a result of this to accelerate progressive deterioration of neuronal functions during aging or exacerbate pre-existing neurodegenerative diseases, such as Alzheimer's disease. With advancing age, the progressive increase in the body's pro-inflammatory status favors the state of vulnerability to both periodontitis and Alzheimer's disease. In the present study, we sought to delineate the roles of cytokines in the pathogenesis of both diseases.MethodsTo examine the impacts of periodontitis on the onset and progression of Alzheimer's disease, 6-month-old female 3 × Tg-AD mice and their age-matched non-transgenic mice were employed. Periodontitis was induced using two different experimental models: heat-killed bacterial-induced periodontitis and ligature-induced periodontitis. To delineate the roles of pro-inflammatory cytokines in the pathogenesis of periodontitis and Alzheimer's disease, interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) were also injected into the buccal mandibular vestibule of mice.ResultsHere, we show that IL-1β and TNF-α were two of the most important and earliest cytokines upregulated upon periodontal infection. The systemic upregulation of these two cytokines promoted a pro-inflammatory environment in the brain contributing to the development of Alzheimer's disease-like pathology and cognitive dysfunctions. Periodontitis-induced systemic inflammation also enhanced brain inflammatory responses and subsequently exacerbated Alzheimer's disease pathology and cognitive impairment in 3 × Tg-AD mice. The role of inflammation in connecting periodontitis to Alzheimer's disease was further affirmed in the conventional magnetization transfer experiment in which increased glial responses resulting from periodontitis led to decreased magnetization transfer ratios in the brain of 3 × Tg-AD mice.ConclusionsSystemic inflammation resulting from periodontitis contributed to the development of Alzheimer's disease tau pathology and subsequently led to cognitive decline in non-transgenic mice. It also potentiated Alzheimer's disease pathological features and exacerbated impairment of cognitive function in 3 × Tg-AD mice. Taken together, this study provides convincing evidence that systemic inflammation serves as a connecting link between periodontitis and Alzheimer's disease.

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Do microbes play a role in Alzheimer's disease?

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Do microbes play a role in Alzheimer's disease?

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