Highlighted papers

Ultrasonic sculpting of virtual optical waveguides in tissue

Chamanzar, M et al.
Nature Communications, published 9 January 2019
https://www.nature.com/articles/s41467-018-07856-w.pdf 

An innovative acousto-optical study published in Nature Communications shows how ultrasound can be used as a virtual wave guide for light signals in biological tissues. Creating ultrasonic standing waves focused the light stimulus and decreased its scattering in deeper tissue layers. Moreover, synchronising laser pulses with the ultrasonic transducer at different phases enabled generation of complex light trajectories. These features may be extremely useful for developing novel methods of brain stimulation/imaging in deep brain structures that would not require invasive manipulations.

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Evangelou, E et al.
Nature Genetics, published 17 September 2018

https://www.nature.com/articles/s41588-018-0205-x 

Elevated blood pressure is a major risk factor for small vessel disease and later life cogntive impairment.  It has an impact on brain structure and function (see H. Suzuki et al., PMID: 29145428).  This work, jointly led by DRI Professor Elliott, reports the largest study of genetic risk factors for hypertension to date.  

 

A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target

Srivastava, P et al.
Nature Communications, Published September 3, 2018

https://www.nature.com/articles/s41467-018-06008-4 

“This provides a novel bioinformatics framework for generating specific hypotheses for new therapeutics by integrating biological and directly pharmacologically-relevant transcriptomics data.  The focus on using pharmacogenomic data related to modulation of GPCRs is intended to better ensure the medicinal chemistry tractability of targets identified.  It also allows tool compounds to be identified that might allow early proofs of principle in human experimental medicine. The demonstration of its application in epilepsy- and, indeed, the target identified- well illustrate the potential of the approach to contribute the research in late life neurodegenerative disease.”

- Professor Paul Matthews
Associate Director UK Dementia Research Institute
Imperial College London

Modulation without surgical intervention

Grossman, N
Science, published 3 August 2018

http://science.sciencemag.org/content/361/6401/461.long 

This personal review provides a short, approachable introduction to UK DRI Fellow Grossman's novel interference transcranial alternating current stimulation method for steerable, targeted deep brain modulation.  Current work now is exploring ways in which this and related methods could be used as safe, low cost interventions to reduce symptoms or therapeutically modify the progression of Alzheimer's and Parkinson's diseases.

Architecture of the Mouse Brain Synaptome

Zhu, F et al.
Neuron, Published August 02, 2018

https://www.cell.com/neuron/fulltext/S0896-6273(18)30581-6

"One of the greatest challenges for studies of neurodegenerative disease is to understand how the functional connectional architecture of the brain changes with loss or damage to neurons; expression of disease depends as much on what is preserved and how it works as it does on what is loss.  This paper provides the most comprehensive description of the connectional architecture of the mouse brain to date.  It provides proofs of concept for developing similar maps with disease models that highlight how the architecture changes.  Moreover, it is scalable enough to allow studies with drugs and other interventions.  I was delighted that one of our UK DRI scientists, Maksym Kopanitsa, was able to contribute to the work of this exceptional team!"

- Professor Paul Matthews
Associate Director UK Dementia Research Institute
Imperial College London

 

Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Davies, G et al.
Nature Communications, published 29 May 2018
https://www.nature.com/articles/s41467-018-04362-x 

This landmark study, extending earlier work using distinct mythology, reported by Imperial's Mike Johnson (PMID: 26691832), discovered almost 150 novel genetic loci contributing to the heritability of cognitive functions. Intriguingly, loci implicated in brain structural determination and neurodegeneration were amongst those identified.

A Prospective Metagenomic and Metabolomic Analysis of the Impact of Exercise & Whey Protein Supplementation on the Gut Microbiome of Sedentary Adults

Cronin, O et al.
mSystems, published 24 April 2018

https://msystems.asm.org/content/3/3/e00044-18

A sedentary lifestyle contributes to risks of sporadic onset, late life Alzheimer's disease. The recent FINGER Trial run by Miia Kivipelto, who divides her time between the Karolinska Institute and Imperial, provides direct evidence that a regular programme of exercise as part of a multi domain intervention reduces risks of later cogntived decline (PMID:29055814).  This report provides a first prospective analysis of the microbiome with exercise interventions, a key step towards elucidating the potential contribution of the microbiome to slowing cognitive decline with ageing. 

Distinguishable brain networks relate disease susceptibility to symptom expression in schizophrenia

Liu, Z et al.
Human Brain Mapping, published 24 April 2018

https://onlinelibrary.wiley.com/doi/full/10.1002/hbm.24190

Using schizophrenia as a model disease, a novel strategy for simultaneous discovery of brain mechanisms contributing to susceptibility and to the variable expression of symptoms of disease was demonstrated.

Single-cell mass cytometry reveals distinct populations of brain myeloid cells in mouse neuroinflammation and neurodegeneration models

Ajami, B et al.
Nature Neuroscience, published 21 April 2018

https://www.nature.com/articles/s41593-018-0100-x

This landmark study led by newly recruited UK DRI Fellow Ajami highlighted alpha5 integrin on myeloid cells as a potential target for therapeutic modulation of neuroinflammatory neurodegeneration, but also showed that animal models of Huntington's Disease and Motor Neuron Disease, despite being associated with brain glial activation, were distinguished from experimental allergic encephalitis by a relative lack of trafficking of blood derived monocytes to the brain.

Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration

Scott, G et al.
Brain, published 1 February 2018

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5837493/

This is an important study suggesting the chronic microglial activation associated with later neurodegeneration and cognitive impairment after head injury may be neuroprotection.  The UK DRI Professor Matthews and colleagues at Imperial, along with UK DRI Professor Zetterberg from UCL, demonstrated that minocycline, administered to inhibit activation of resident microglia, enhances NfL release, an index of neurodegeneration. 

Abnormal brain white matter microstructure is associated with both pre-hypertension and hypertension

Suzuki, H et al.
PLoS One, published 16 November 2017

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0187600&type=printable 

In the largest brain imaging study of hypertension to date, white matter pathology was identified even with pre-hypertension, emphasising that sustained elevation of blood pressure even to levels previously considered as within a healthy range, can contribute to brain injury and cognitive decline.