Enhancing axonal transport in vivo as a therapeutic strategy for Alzheimer's disease

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

A nerve cell can be compared to a telephone (the fixed line variety) and it's wire connects it to other phones. The phone sends messages into the wire, but without the wire they go nowhere and the phone is useless. However, these are living wires (axons), which need a constant supply of nutrients and proteins to keep them in good shape. These nutrients are made within the telephone (the cell body) and channelled along the wires by a miniature transport system. Waste products and survival signals travel in the opposite direction. In one of the most remarkable achievements of the human body, 100 billion nerve cells work day and night sending thousands of packages down wires up to a metre long but microscopically narrow, and we don’t even know it’s happening until it goes wrong. Like any supply chain, from frozen water pipes to army convoys, this system is vulnerable. Defective transport is a major reason why nerve cells and their wires die in Alzheimer’s disease and other dementias. With the ART’s support we have studied how the transport system gets blocked. With that work now published, we are turning our attention to how to keep it running. We have found a way to boost transport in healthy mice, and with new funding we can test whether this reduces amyloid pathology and the damage to wires. We will also investigate whether human genes link the transport system to Alzheimer’s and how this might be prevented.

Publications

10 25 50
 
Description We found that genetic mutations that cause Alzheimer's disease and frontotemporal dementia interact to significantly impair axonal transport. However, this did not affect disease outcome.
Exploitation Route As our original hypothesis was disproven we have switched the focus of our Alzheimer's disease research to studying amyloid pathology in organotypic slices.
Sectors Healthcare

 
Description Multiple presentations to lay audiences (Alzheimer public meetings, ageing public meeting, Schools, Science Festival, etc)
First Year Of Impact 2012
Sector Education
Impact Types Societal

 
Description ARUK studentship
Amount £110,447 (GBP)
Funding ID ARUK-PhD2013-13 
Organisation Alzheimer's Research UK 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2013 
End 09/2016
 
Description Alzheimer's Research UK Cambridge Network Public Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact A wide selection of the public were better informed of current research in dementia, from school children children considering careers in research or dementia care to early stage patients and their carers and relatives.

We had several follow-up requests for talks at local events that will be followed up over the coming months
Year(s) Of Engagement Activity 2014,2016
 
Description Café Scientifique presentation (Cambridge 2012) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Many people attended talk entitled "keeping your nerves".

Positive feedback about research
Year(s) Of Engagement Activity 2012
 
Description Cambridge Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Lots of interest in our axon transport exhibit

Exhibit has been used at multiple events since, including pint of science and school visits
Year(s) Of Engagement Activity 2015
 
Description Coordinating/ Administering ARUK Cambridge Network 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact We have been involved in organising numerous events including scientific and public meetings. We have made descisions on funding local projects and conference attendance.

Much local research in the area has been funded. There have been numerous successful meetings.
Year(s) Of Engagement Activity 2013,2014,2015,2016,2017
 
Description Multiple Lab Tours (High value donors and Park Run) 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Supporters
Results and Impact Open discussions about animal research as well as how money donated to ARUK funds research.

Positive feedback from both tours. First tour given resulted in a second tour with another group being organised
Year(s) Of Engagement Activity 2014,2015
 
Description Presentation at Bedford Mental Health Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Health professionals
Results and Impact Talk was well recieved and sparked discussion

Discussion of scientific methods to a largely medical audience
Year(s) Of Engagement Activity 2015
 
Description Presentation to Hills Road 6th Form College 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Lots of discussion afterwards about Alzheimer's Disease and the use of animals in research. Very positive feedback and students followed up with further emailed questions.

A number of students who were doing extended research projects on Alzheimer's Disease asked further questions by email.
Year(s) Of Engagement Activity 2015
 
Description Public discussion (Cambridge, UK 2012) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Informed Q&A session with a panel of experts and members of the public about aging research

Useful feedback
Year(s) Of Engagement Activity 2012
 
Description Radio/podcast interview (BBC Radio Cambridgeshire, 2012) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact Not quantifiable

Positive feedback from people who had heard the broadcast
Year(s) Of Engagement Activity 2012
 
Description Talk about preclinical models of Alzheimer's Disease 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Health professionals
Results and Impact Good questions and positive feedback

Forged relationships with non scientific members of the network
Year(s) Of Engagement Activity 2015
 
Description Understanding Animal Research Institute Lay Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Much discussion afterwards. Positive feedback from non-scientific staff at the institute

Invited to talk at Hills Road Sixth Form College
Year(s) Of Engagement Activity 2015