Infection of Fungi and Bacteria in Brain Tissue From Elderly Persons and Patients With Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia in elderly people. The etiology of this disease remains a matter of intensive research in many laboratories. We have advanced the idea that disseminated fungal infection contributes to the etiology of AD. Thus, we have demonstrated that fungal proteins and DNA are present in nervous tissue from AD patients. More recently, we have reported that bacterial infections can accompany these mycoses, suggesting that polymicrobial infections exist in AD brains. In the present study, we have examined fungal and bacterial infection in brain tissue from AD patients and control subjects by immunohistochemistry. In addition, we have documented the fungal and bacterial species in brain regions from AD patients and control subjects by next-generation sequencing (NGS). Our results from the analysis of ten AD patients reveal a variety of fungal and bacterial species, although some were more prominent than others. The fungal genera more prevalent in AD patients were Alternaria, Botrytis, Candida, and Malassezia. We also compared these genera with those found in elderly and younger subjects. One of the most prominent genera in control subjects was Fusarium. Principal component analysis clearly indicated that fungi from frontal cortex samples of AD brains clustered together and differed from those of equivalent control subjects. Regarding bacterial infection, the phylum Proteobacteria was the most prominent in both AD patients and controls, followed by Firmicutes, Actinobacteria, and Bacteroides. At the family level, Burkholderiaceae and Staphylococcaceae exhibited higher percentages in AD brains than in control brains. These findings could be of interest to guide targeted antimicrobial therapy for AD patients. Moreover, the variety of microbial species in each patient may constitute a basis for a better understanding of the evolution and severity of clinical symptoms in each patient.

Fecal Microbiota Transplantation in Neurological Disorders

“…Studies have demonstrated the presence of microorganisms in brains of both AD patients and healthy controls. However, increased LPS levels (Zhan et al, 2016; and an increased presence of several bacteria and fungi, including some gut commensals, were observed in brains of AD patients compared to controls (Mawanda and Wallace, 2013;Pisa et al, 2017;Alonso et al, 2018;Dominy et al, 2019). The presence of bacterial LPS or endotoxin-mediated inflammation contributes to amyloid neurotoxicity .…”

Linking molecular pathways and large-scale computational modeling to assess candidate disease mechanisms and pharmacodynamics in Alzheimer’s disease

“…adding mathematical models that describe how molecular changes alter population activity -so called cause--and--effect models. We will focus here on the disrupted inhibitory function of interneurons and consecutive hyperexcitability caused by Abeta -while we are aware of various other factors with potential roles for AD aetiology, such as vascular changes (19--21), neuroinflammation (22--25), genetics (26--28), environmental factors (29,30) and concomitant proteinopathies others than Abeta pathology (31,32). Beside Abeta there is a second molecular hallmark associated with the pathogenesis of AD: the phosphorylated Tau 'tubulin--associated unit' protein (8,33,34) which contributes to microtubule stability in the neural cytoskeleton (34).…”

Fungal communities (Mycobiome) as potential ecological indicators within confluence stretch of Ganges and Yamuna Rivers, India

“…Several metabolic functions like biosynthesis of secondary metabolites and amino acid, carbohydrate, energy, lipid, cofactors and vitamins, terpenoids and polyketides, nucleotide and xenobiotic biodegradation and metabolism were observed in the analysis. There are several reports on occurrence of fungi in different regions of brain tissues and blood vessels, recovered from the patients suffering Alzheimer’s disease and Parkinson’s disease (Pisa et al 2015; Alonso et al 2017, 2018). Addressing this aspect, we emphasized our analysis towards the functional profile of the autochthonous and the allochthonous fungal communities.…”