The role of the gut microbiome in cognitive function and Alzheimer’s disease

Abstract The prevalence of dementia increases significantly from the age of 65 years, doubling every five years thereafter. Alzheimer's disease (AD) and vascular dementia (VaD) constitute the two main dementia types. Differentiating them encompasses anamnesis, neurological examination, laboratory and neuroimaging exams and neuropsychological assessment. Neuropsychological assessment produces different findings for each dementia type, and reveals those areas most impaired as well as those most preserved. The aim of the present article was to describe the role of neuropsychology in diagnosing dementia and achieving a differential diagnosis between AD and VaD. A general overview follows of the most widely known instruments used to assess cognitive function in dementia, and the cognitive changes seen in AD and VaD. The conclusion drawn was that there is significant overlap in cognitive changes between both these dementia types, while each type has its own specific characteristics which are identifiable and quantifiable on neuropsychological assessments and provide the basis for reaching a differential diagnosis.

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The Endocannabinoid System: A Bridge between Alzheimer’s Disease and Gut Microbiota

Life ◽

10.3390/life11090934 ◽

2021 ◽

Vol 11 (9) ◽

pp. 934

Author(s):

Tiziana Bisogno ◽

Anna Lauritano ◽

Fabiana Piscitelli

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiota ◽

Cognitive Deficits ◽

Gut Microbiome ◽

Endocannabinoid System ◽

Severe Dementia ◽

System A ◽

Preclinical Ad

Alzheimer’s disease (AD) is a neurodegenerative disease that progresses from mild cognitive impairment to severe dementia over time. The main clinical hallmarks of the disease (e.g., beta-amyloid plaques and neurofibrillary tangles) begin during preclinical AD when cognitive deficits are not yet apparent. Hence, a more profound understanding of AD pathogenesis is needed to develop new therapeutic strategies. In this context, the endocannabinoid (eCB) system and the gut microbiome are increasingly emerging as important players in maintaining the general homeostasis and the health status of the host. However, their interaction has come to light just recently with gut microbiota regulating the eCB tone at both receptor and enzyme levels in intestinal and adipose tissues. Importantly, eCB system and gut microbiome, have been suggested to play a role in AD in both animal and human studies. Therefore, the microbiome gut-brain axis and the eCB system are potential common denominators in the AD physiopathology. Hence, the aim of this review is to provide a general overview on the role of both the eCB system and the microbiome gut-brain axis in AD and to suggest possible mechanisms that underlie the potential interplay of these two systems.

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The role of Alzheimer’s disease polygenic risk scores in changes of cognitive function in older adults: A longitudinal cohort study

Alzheimer s & Dementia ◽

10.1002/alz.037853 ◽

2020 ◽

Vol 16 (S3) ◽

Author(s):

Gongbu Pan ◽

Anna E. King ◽

Aidan Bindoff ◽

Mathew J. Summers ◽

James C. Vickers ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cohort Study ◽

Cognitive Function ◽

Longitudinal Cohort Study ◽

Risk Scores ◽

Longitudinal Cohort ◽

Polygenic Risk

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Role of BACE1 in Cognitive Function, from Alzheimer’s Disease to Traumatic Brain Injury

Genes, Environment and Alzheimer's Disease ◽

10.1016/b978-0-12-802851-3.00008-5 ◽

2016 ◽

pp. 239-266

Author(s):

Sylvia Lombardo ◽

Giuseppina Tesco

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Cognitive Function

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The Role of Higher-Level Cognitive Function in Gait: Executive Dysfunction Contributes to Fall Risk in Alzheimer’s Disease

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000105126 ◽

2007 ◽

Vol 24 (2) ◽

pp. 125-137 ◽

Cited By ~ 171

Author(s):

Pamela L. Sheridan ◽

Jeffrey M. Hausdorff

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Fall Risk ◽

Executive Dysfunction

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Role of RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer's Disease

10.1101/2021.09.20.461132 ◽

2021 ◽

Author(s):

Sanjay Awasthi ◽

Ashly Hindle ◽

Neha Sawant ◽

Mathew George ◽

Murali Vijayan ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Function ◽

Mitochondrial Dysfunction ◽

Mitochondrial Function ◽

Sensory Function ◽

Expression Of Genes

The purpose of our study is to understand the role of the Ralbp1 gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer's disease (AD) pathogenesis. The Ralbp1 gene encodes the 76 kDa protein Rlip (aka RLIP76). Previous studies have revealed its role in OS-related cancer. However, Rlip is transcriptionally regulated by EP300, a CREB-binding protein that is important for synaptic plasticity in the brain. Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. OS causes rapid cellular accumulation of Rlip and its translocation from a tubulin-bound complex to the plasma membrane, mitochondria and nucleus. Therefore, Rlip may play an important role in maintaining cognitive function in the face of OS-related injury. This study is aimed to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype and Rlip+/- mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in mouse brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, inhibition of stress-activated gene expression, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues of these mice. Furthermore, we compared the cognitive function of wildtype and Rlip+/- mice. Behavioral, basic motor and sensory function tests in Rlip+/- mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function, and CREB signaling genes in the Rlip+/- mouse liver. Our results suggest that the Rlip deficiency-associated increase in OS and mitochondrial dysfunction could contribute to the development of OS-related AD processes. Therefore, the restoration of Rlip activity and endogenous cytoprotective mechanisms by pharmacological interventions is a novel approach to protect against AD.

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