Exploring the Gut-Brain Axis in Ageing and Neurodegeneration

Summary

Neurodegenerative diseases are a major health concern due to their growing societal implications and economic costs. The identification of early markers of pathogenic mechanisms is one of the current main challenges. The gut-brain axis has become a primary target because of its transversal role across the neurodegenerative spectrum and its effect on cognition. However, despite recent progress, how changes in the gut-microbiota composition can affect the human brain is still unclear.

The goal of this observational study is to characterise the gut-microbiota composition associated with alterations in brain structure and function during the ageing process and across neurodegenerative disorders. This is based on recent studies showing that changes in the human brain and in the microbiota composition, can indicate very sensitively and in a predictive way pathological development and, consequently, be used as markers of neurodegenerative diseases.

The main questions it aims to answer are:

* How variation in the gut-microbiota composition correlates with the normal brain ageing trajectory?
* How dysregulation in the gut-microbiota correlates with pathological changes in brain regions in specific neurodegenerative disorders?
* Can the impact of the gut-microbiota on the brain be modulated by blood biomarkers?

The investigators will recruit 40 young healthy participants, 40 old healthy participants, 40 participants with prodromal Alzheimer's Disease, 40 participants with Parkinson's Disease and 40 participants with Multiple Sclerosis.

Participants will undergo the following examinations:

* Magnetic Resonance Imaging
* Analysis of a stool sample
* Analysis of a blood sample
* Neuropsychological assessment
* Questionnaires on eating habits

Conditions

• Healthy
• Prodromal Alzheimer's Disease
• Parkinson Disease
• Multiple Sclerosis

Interventions

DIAGNOSTIC_TEST

Magnetic Resonance Imaging

The Magnetic Resonance Imaging protocol will comprise both structural and functional sequences.

BEHAVIORAL

Neuropsychological protocol

Neuropsychological tests will be administered to participants to assess general cognitive state and a range of high-level cognitive functions (memory, executive, language). In addition, disease-specific tests will be administered to patients to investigate disease staging and the level of disability and autonomy.

BEHAVIORAL

Eating habits

Information on eating habits will be derived from food questionnaires.

DIAGNOSTIC_TEST

Microbiome analyses

The Microbiome analyses will be derived from a stool sample (16S rRNA sequencing targeted metagenomic analyses).

DIAGNOSTIC_TEST

Inflammatory markers

Inflammatory markers will be evaluated in terms RNA expression level in plasma blood sample.

DIAGNOSTIC_TEST

Alzheimer's Disease biomarkers

The Alzheimer's Disease biomarkers will be measured in the plasma of prodromal Alzheimer's Disease patients.

Sponsors & Collaborators

• IRCCS Centro San Giovanni di Dio Fatebenefratelli

  collaborator OTHER

• Università Ca' Foscari Venezia

  collaborator UNKNOWN

• IRCCS San Camillo, Venezia, Italy

  lead OTHER

Principal Investigators

• Nicola Filippini · IRCCS San Camillo, Venezia, Italy

Eligibility

Min Age

20 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-05-01

Primary Completion

2027-04-30

Completion

2027-04-30

Countries

• Italy

Study Locations