scholarly journals Diet-Microbiota-Brain Axis in Alzheimer’s Disease

2021 ◽  
pp. 1-7
Author(s):  
Halle J. Kincaid ◽  
Ravinder Nagpal ◽  
Hariom Yadav

<b><i>Background:</i></b> Alzheimer’s disease (AD) is the most common form of dementia, particularly in older adults, with clinical manifestations of progressive cognitive decline and functional impairment. The prevalence of AD and related dementia is mounting worldwide, but its etiology remains unresolved, with no available preventative or ameliorative therapy. Emerging evidence suggests that the gut microbiota of patients with AD is different from cognitively normal counterparts. <b><i>Summary:</i></b> Communication between gut and brain (gut-brain axis) plays a crucial role in AD pathology. Bacteria inhabiting the gut strongly influence this gut-brain axis and thus may participate in AD pathology. Diet, one of the strongest modulators of gut microbiota, also strongly influences brain health and AD pathology. Gut microbiota metabolites including short-chain fatty acids, pro-inflammatory factors, and neurotransmitters may also affect AD pathogenesis and associated cognitive decline. Therefore, investigation of diet-microbiota-brain axis is important to better understand its contribution in AD pathology and its potential use as a target to prevent and treat AD. Herein, we discuss the link between AD and gut microbiota and ponder how microbiota modulation through nutritional approaches may offer avenues for discovering novel preventive and therapeutic strategies against AD. <b><i>Key Message:</i></b> A strong association exists between lifestyle factors and AD prevalence wherein unhealthy dietary factors have been linked to neurodegeneration. Specific prudent dietary patterns might help in preventing or delaying AD progression by affecting β-amyloid production and tau processing and regulating AD-associated inflammation, metabolism and oxidative stress, plausibly via modulating gut microbiota.

2021 ◽  
pp. 1-20
Author(s):  
Daniel Cuervo-Zanatta ◽  
Jaime Garcia-Mena ◽  
Claudia Perez-Cruz

Background: Normal aging is accompanied by cognitive deficiencies, affecting women and men equally. Aging is the main risk factor for Alzheimer’s disease (AD), with women having a higher risk. The higher prevalence of AD in women is associated with the abrupt hormonal decline seen after menopause. However, other factors may be involved in this sex-related cognitive decline. Alterations in gut microbiota (GM) and its bioproducts have been reported in AD subjects and transgenic (Tg) mice, having a direct impact on brain amyloid-β pathology in male (M), but not in female (F) mice. Objective: The aim of this work was to determine GM composition and cognitive dysfunction in M and F wildtype (WT) and Tg mice, in a sex/genotype segregation design. Methods: Anxiety, short term working-memory, spatial learning, and long-term spatial memory were evaluated in 6-month-old WT and Tg male mice. Fecal short chain fatty acids were determined by chromatography, and DNA sequencing and bioinformatic analyses were used to determine GM differences. Results: We observed sex-dependent differences in cognitive skills in WT mice, favoring F mice. However, the cognitive advantage of females was lost in Tg mice. GM composition showed few sex-related differences in WT mice. Contrary, Tg-M mice presented a more severe dysbiosis than Tg-F mice. A decreased abundance of Ruminococcaceae was associated with cognitive deficits in Tg-F mice, while butyrate levels were positively associated with better working- and object recognition-memory in WT-F mice. Conclusion: This report describes a sex-dependent association between GM alterations and cognitive impairment in a mice model of AD.


2020 ◽  
Vol 11 (1) ◽  
pp. 79-89 ◽  
Author(s):  
F.H.P. Tan ◽  
G. Liu ◽  
S.-Y.A. Lau ◽  
M.H. Jaafar ◽  
Y.-H. Park ◽  
...  

Alzheimer’s disease (AD) is a progressive disease and one of the most common forms of neurodegenerative disorders. Emerging evidence is supporting the use of various strategies that modulate gut microbiota to exert neurological and psychological changes. This includes the utilisation of probiotics as a natural and dietary intervention for brain health. Here, we showed the potential AD-reversal effects of Lactobacillus probiotics through feeding to our Drosophila melanogaster AD model. The administration of Lactobacillus strains was able to rescue the rough eye phenotype (REP) seen in AD-induced Drosophila, with a more prominent effect observed upon the administration of Lactobacillus plantarum DR7 (DR7). Furthermore, we analysed the gut microbiota of the AD-induced Drosophila and found elevated levels of Wolbachia. The administration of DR7 restored the gut microbiota diversity of AD-induced Drosophila with a significant reduction in Wolbachia’s relative abundance, accompanied by an increase of Stenotrophomonas and Acetobacter. Through functional predictive analyses, Wolbachia was predicted to be positively correlated with neurodegenerative disorders, such as Parkinson’s, Huntington’s and Alzheimer’s diseases, while Stenotrophomonas was negatively correlated with these neurodegenerative disorders. Altogether, our data exhibited DR7’s ability to ameliorate the AD effects in our AD-induced Drosophila. Thus, we propose that Wolbachia be used as a potential biomarker for AD.


2021 ◽  
Vol 15 ◽  
Author(s):  
Paola C. Bello-Medina ◽  
Fernando Hernández-Quiroz ◽  
Marcel Pérez-Morales ◽  
Diego A. González-Franco ◽  
Guadalupe Cruz-Pauseno ◽  
...  

The irreversible and progressive neurodegenerative Alzheimer’s disease (AD) is characterized by cognitive decline, extracellular β-amyloid peptide accumulation, and tau neurofibrillary tangles in the cortex and hippocampus. The triple-transgenic (3xTg) mouse model of AD presents memory impairment in several behavioral paradigms and histopathological alterations from 6 to 16 months old. Additionally, it seems that dysbiotic gut microbiota is present in both mouse models and patients of AD at the cognitive symptomatic stage. The present study aimed to assess spatial learning, memory retention, and gut microbiota alterations in an early adult stage of the 3xTg-AD mice as well as to explore its sexual dimorphism. We evaluated motor activity, novel-object localization training, and retention test as well as collected fecal samples to characterize relative abundance, alpha- and beta-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) analysis in gut microbiota in both female and male 3xTg-AD mice, and controls [non-transgenic mice (NoTg)], at 3 and 5 months old. We found spatial memory deficits in female and male 3xTg-AD but no alteration neither during training nor in motor activity. Importantly, already at 3 months old, we observed decreased relative abundances of Actinobacteria and TM7 in 3xTg-AD compared to NoTg mice, while the beta diversity of gut microbiota was different in female and male 3xTg-AD mice in comparison to NoTg. Our results suggest that gut microbiota modifications in 3xTg-AD mice anticipate and thus could be causally related to cognitive decline already at the early adult age of AD. We propose that microbiota alterations may be used as an early and non-invasive diagnostic biomarker of AD.


2018 ◽  
Author(s):  
Daniel Felsky ◽  
Tina Roostaei ◽  
Kwangsik Nho ◽  
Shannon L. Risacher ◽  
Elizabeth M. Bradshaw ◽  
...  

AbstractMicroglia, the resident immune cells of the brain, have important roles in brain health. However, little is known about the regulation and consequences of microglial activation in the aging human brain. We assessed the effect of microglial activation in the aging human brain by calculating the proportion of activated microglia (PAM), based on morphologically defined stages of activation in four regions sampled postmortem from up to 225 elderly individuals. We found that cortical and not subcortical PAM measures were strongly associated with β-amyloid, tau-related neuropathology, and rates of cognitive decline. Effect sizes for PAM measures are substantial, comparable to that of APOE ɛ4, the strongest genetic risk factor for Alzheimer’s disease. Mediation modeling suggests that PAM accelerates accumulation of tau pathology leading to cognitive decline, supporting an upstream role for microglial activation in Alzheimer’s disease. Genome-wide analyses identified a common variant (rs2997325) influencing cortical PAM that also affected in vivo microglial activation measured by positron emission tomography using [11C]-PBR28 in an independent cohort. Finally, we identify overlaps of PAM’s genetic architecture with those of Alzheimer’s disease, educational attainment, and several other traits.


2021 ◽  
Vol 33 (S1) ◽  
pp. 90-91
Author(s):  
Alena Sidenkova

IntroductionThe aging processes are accelerating in all regions of the world. The involvement of older people in production and social processes determines the need to maintain a high level of social and psychological adaptation, despite the progressive pathology of the brain caused by its aging. This increases the relevance of research related to the study of biological reserves of the brain and psychological and social mechanisms of human adaptation in late adulthood. The risk of developing cognitive disorders is not fatal. According to some observations, even in the hippocampal type of UKR, despite the content of amyloid in the brain, the functional and social activity of the elderly remains high. Prospective studies show that people with high cognitive reserve have a lower risk of developing dementia. Cognitive reserve is the brain’s resistance to damage. Cognitive reserve is the ability of the brain to cope with the consequences of damage caused by external influences, brain stroke, chronic brain ischemia, neurodegenerative diseases, and age-related changes. Cognitive reserve is the brain’s ability to functionally compensate for and minimize clinical manifestations of cognitive impairment. The mechanisms of cognitive reserve in normal and Alzheimer’s disease are different. In healthy older adults, a higher cognitive reserve correlates with larger brain sizes and effective strategies for performing cognitive tasks. In the early stages of Alzheimer’s disease and Alzheimer’s disease, the size of the brain decreases. But high brain activity helps preserve cognitive resources. Excessive brain activity in dementia is a compensatory mechanism. This is confirmed by the results of functional magnetic resonance imaging of the brain. Of course, the degree of brain atrophy is a predisposing factor for dementia, but it is not a mandatory factor for cognitive decline. So, the symptoms of dementia do not appear until you have crossed the critical border of damage to the brain substance. Progressive brain atrophy underlies the clinical manifestations of dementia in neurodegenerative diseases, but the correlation between the degree of brain damage and cognitive impairment is not linear.Research materials and methodsAn observational 10-year longitudinal study was conducted. In 2006, moderate cognitive impairment was found in 66 patients. The group of patients included 49 women and 49 men. Their average age in 2006 was 59.3±5.2 years. In 2006, the severity of cognitive decline was 26.2±1.9 points on the MMSE scale. This corresponds to indicators of moderate cognitive impairment. Research methods: clinical and psychopathological, psychometric, statistical. Questionnaire “Loss and acquisition of personal resources” (N. Vodopyanova, M. Stein), MMSE scale.Research resultIn 2006, amyloid was detected in the spinal fluid of all patients selected for the study group. If a patient developed dementia, they were given specific therapy. The dynamics of cognitive functions in patients was different. Mild dementia was formed in 53% of patients. Moderate dementia was formed in 10.6% of patients. Moderate cognitive impairment (pre-dementia) persisted in 36.4% of patients. Hereditary burden of dementia in patients with moderate dementia was detected 2 times more often. Back in 2006, we identified the leading sensory systems of patients. The master sensor system determines the modality of the main information flow. This is the most important part of the information that a person interacts with. This is the basis of interaction with reality. This is the basis of cognitive functions. Correlations of age-specific lesions of the corresponding sensory systems with the severity of cognitive decline were found in patients with the corresponding sensory modality (Spearman’s Correlation Coefficient-r, p<0.05): presbyacoussis – auditory r=0.667, presbyopia-visual r=0.705. The influence of psychosocial factors on the condition of patients was studied. In dementia, significant history of psychotrauma was found in 35.7%. Moderate stress was detected in the group of patients with moderate cognitive impairment in 33.3%. Moderate stress was detected in the group of patients with dementia in 83.3%. Stress of loss of life meaning was detected more often in patients with dementia 76.7%. It is important not only what stresses a person endures, but how they can cope with them. Dementia patients were statistically more likely to have unproductive coping strategies that did not help them cope adequately with stress.ConclusionsThe concept of cognitive reserve suggests possible causes of heterogeneity in the dynamics of cognitive decline in the initial stages of atrophic-degenerative brain diseases: biological causes and psychosocial causes. The concept of cognitive reserve helps to study and develop individual programs for the prevention of severe cognitive disorders.


2021 ◽  
Vol 12 (1) ◽  
pp. 581-600
Author(s):  
Si-Ran Zhong ◽  
Qi Kuang ◽  
Fan Zhang ◽  
Ben Chen ◽  
Zhen-Guo Zhong

Abstract Increasing scientific evidence demonstrates that the gut microbiota influences normal physiological homeostasis and contributes to pathogenesis, ranging from obesity to neurodegenerative diseases, such as Alzheimer’s disease (AD). Gut microbiota can interact with the central nervous system (CNS) through the microbiota-gut-brain axis. The interaction is mediated by microbial secretions, metabolic interventions, and neural stimulation. Here, we review and summarize the regulatory pathways (immune, neural, neuroendocrine, or metabolic systems) in the microbiota-gut-brain axis in AD pathogenesis. Besides, we highlight the significant roles of the intestinal epithelial barrier and blood–brain barrier (BBB) in the microbiota-gut-brain axis. During the progression of AD, there is a gradual shift in the gut microbiota and host co-metabolic relationship, leading to gut dysbiosis, and the imbalance of microbial secretions and metabolites, such as lipopolysaccharides (LPS) and short-chain fatty acids (SCFAs). These products may affect the CNS metabolic state and immune balance through the microbiota-gut-brain axis. Further, we summarize the potential microbiota-gut-brain axis-targeted therapy including carbohydrates, probiotics, dietary measures, and propose new strategies toward the development of anti-AD drugs. Taken together, the data in this review suggest that remodeling the gut microbiota may present a tractable strategy in the management and development of new therapeutics against AD and other neurodegenerative diseases.


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 361
Author(s):  
Friedrich Leblhuber ◽  
Daniela Ehrlich ◽  
Kostja Steiner ◽  
Simon Geisler ◽  
Dietmar Fuchs ◽  
...  

The microbiota–gut–brain axis plays an important role in the development of neurodegenerative diseases. Commensal and pathogenic enteric bacteria can influence brain and immune system function by the production of lipopolysaccharides and amyloid. Dysbiosis of the intestinal microbiome induces local and consecutively systemic immune-mediated inflammation. Proinflammatory cytokines then trigger neuroinflammation and finally neurodegeneration. Immune-mediated oxidative stress can lead to a deficiency of vitamins and essential micronutrients. Furthermore, the wrong composition of gut microbiota might impair the intake and metabolization of nutrients. In patients with Alzheimer’s disease (AD) significant alterations of the gut microbiota have been demonstrated. Standard Western diet, infections, decreased physical activity and chronic stress impact the composition and diversity of gut microbiota. A higher abundancy of “pro-inflammatory” gut microbiota goes along with enhanced systemic inflammation and neuroinflammatory processes. Thus, AD beginning in the gut is closely related to the imbalance of gut microbiota. Modulation of gut microbiota by Mediterranean diet, probiotics and curcumin can slow down cognitive decline and alter the gut microbiome significantly. A multi-domain intervention approach addressing underlying causes of AD (inflammation, infections, metabolic alterations like insulin resistance and nutrient deficiency, stress) appears very promising to reduce or even reverse cognitive decline by exerting positive effects on the gut microbiota.


Author(s):  
Jean François Dartigues ◽  
Leslie Grasset ◽  
Tabue Teguo Maturin ◽  
Alexandra Foubert ◽  
Karine Pérès ◽  
...  

The epidemiology of Alzheimer’s disease (AD) is difficult for several reasons: lack of operational criteria for AD; majority of incident cases occurring in very old people with multiple comorbidities; long prodromal phase before the dementia phase; large proportion of undiagnosed cases; and strong competition with death. There is no clear operational definition of cognitive decline and of impairment in social function related to this decline, and these clinical manifestations are the core of the clinical diagnosis of AD. Diagnosis is left to the the clinician’s subjectivity, which is influenced by the cultural context, the social context, and the expected efficacy of the treatment at the early phase of dementia. Several published papers are presented and conclusions discussed, including the protective effect of playing board games, the effect of changes in leisure activities with age, natural history of cognitive decline before AD according to education, and predictive score for dementia.


Author(s):  
Marco Bucci ◽  
Konstantinos Chiotis ◽  
Agneta Nordberg ◽  

AbstractFor early detection of Alzheimer’s disease, it is important to find biomarkers with predictive value for disease progression and clinical manifestations, such as cognitive decline. Individuals can now be profiled based on their biomarker status for Aβ42 (A) or tau (T) deposition and neurodegeneration (N). The aim of this study was to compare the cerebrospinal fluid (CSF) and imaging (PET/MR) biomarkers in each ATN category and to assess their ability to predict longitudinal cognitive decline. A subset of 282 patients, who had had at the same time PET investigations with amyloid-β and tau tracers, CSF sampling, and structural MRI (18% within 13 months), was selected from the ADNI dataset. The participants were grouped by clinical diagnosis at that time: cognitively normal, subjective memory concern, early or late mild cognitive impairment, or AD. Agreement between CSF (amyloid-β-1-42(A), phosphorylated-Tau181(T), total-Tau(N)), and imaging (amyloid-β PET (florbetaben and florbetapir)(A), tau PET (flortaucipir)(T), hippocampal volume (MRI)(N)) positivity in ATN was assessed with Cohen’s Kappa. Linear mixed-effects models were used to predict decline in the episodic memory. There was moderate agreement between PET and CSF for A biomarkers (Kappa = 0.39–0.71), while only fair agreement for T biomarkers (Kappa ≤ 0.40, except AD) and discordance for N biomarkers across all groups (Kappa ≤ 0.14) was found. Baseline PET tau predicted longitudinal decline in episodic memory irrespective of CSF p-Tau181 positivity (p ≤ 0.02). Baseline PET tau and amyloid-β predicted decline in episodic memory (p ≤ 0.0001), but isolated PET amyloid-β did not. Isolated PET Tau positivity was only observed in 2 participants (0.71% of the sample). While results for amyloid-β were similar using CSF or imaging, CSF and imaging results for tau and neurodegeneration were not interchangeable. PET tau positivity was superior to CSF p-Tau181 and PET amyloid-β in predicting cognitive decline in the AD continuum within 3 years of follow-up.


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