I received my PhD at the University of Dundee in 2010, focused on the pharmacology and signalling of potentially novel cannabinoid receptors. I then spent my first postdoctoral position in the lab or Dr. Istvan Katona in Budapest, assessing the nanoscale distribution of synaptic proteins in a mouse model of Fragile X Syndrome, funded by an EMBO long-term fellowship. With the aim of building upon my technical expertise, I moved to the lab of Dr. Tara Spires-Jones at the University of Edinburgh in 2014 and in 2016 was awarded a 3yr project grant from MND Scotland as a PostDoc. In May 2019 I moved to the University of Dundee to establish my own group and continue my research on synaptic pathology in health and disease.

In 2023 I was awarded a Dementia Research Leaders Fellowship from the Alzheimer's Society and a Springboard Award from the Academy of Medical Sciences.

Alzheimer’s disease, Frontotemporal Dementia (FTD) and Motor Neuron Disease (MND) are diseases of the brain, that at first glance have very different symptoms. Alzheimer’s disease usually causes memory problems first, FTD affects personality, behaviour, and language and MND affects the ability to move. However, people with FTD and people with MND share some common symptoms. One in every two people with the most common form of MND (called Amyotrophic Lateral Sclerosis (ALS)) have problems with their thinking and language skills, in a similar way to people with FTD. Also, one in every two people with FTD have problems with movement. This similarity in symptoms can be so strong that more than one in every ten people with ALS also have FTD.

Importantly, Alzheimer’s disease, FTD and ALS all share some common changes in the brain. All three show a loss of brain cells (neurons), which causes the brain to shrink, and this has a big effect on how the brain works. However, brain shrinkage is normally only seen when someone has had the disease for a long time, so it is very important that we understand the earlier disease steps that lead to shrinkage, so we can design drugs to stop it.

Synapses are the connection points between neurons, and they help send information from one neuron to another (Henstridge et al. 2016 Ageing Research Reviews). We have more synapses in our brain than there are stars in our galaxy and their health is important for making sure our brain works properly. Despite their importance for normal brain function we still don’t fully know how they work or what happens to them in diseases that cause dementia.

However, research suggests that synapses break down very early in disease, possibly even before people show signs of having it. Synapse loss occurs before neurons die (Henstridge et al. 2016 Ageing Research Reviews), so they could be targeted with new drugs to keep them safe and stop the death of neurons. First we need to know a lot more about where, when, and why synapses are being lost.

What have we discovered?

Using a special technique that allows us to cut human brain into slices 1000x thinner than the thickness of a human hair (called Array Tomography (Sanchez Avila and Henstridge 2022), we have been able to count synapses in different parts of the brain.

This approach allowed us to show for the first time that a lower number of synapses in a frontal region of the brain, associated with worse thinking skills in people with ALS (Henstridge et al. 2018 Acta Neuropathologica).

Following this observation that synapse number was lower in the frontal part of the brain, we wanted to know what was driving that synapse loss. To address this question we employed a technique called proteomics, which allows us to look at all the building blocks (proteins) within the synapse. We collected synapses from donated brains of people with or without ALS and performed proteomics. We discovered hundreds of proteins that changed in people with ALS. Importantly, we could also identify changes that occurred in people with ALSci and in those people that had a C9ORF72 repeat expansion, the most common genetic form of ALS (Laszlo et al. 2022 Acta Neuropathologica Communications).

More recently, we have used this proteomics approach to analyse synapses in the spinal cord of people with ALS. Importantly, we compared our data with similar proteomics data from human cells from ALS patients grown in a dish, to try and identify similarities. Working in collaboration with colleagues in Ulm, Germany we identified a group of proteins in the synapse that decreased in ALS spinal cord and cells in a dish. These proteins are found in the presynapse and are critical for the release of neurotransmitters (Aly and Laszlo et al. 2023 Acta Neuropathologica).

Importantly, by preserving synaptic health and number in the cells in a dish, we could keep the patient-derived cells alive for longer. This may highlight a new way to treat ALS and potentially other neurodegenerative diseases.

The lab continues to use array tomography and proteomics to investigate changes in the diseased human synapse. We also employ several other techniques to study how different types of brain cell can damage synapses and possibly drive disease.

• Aly, A., Laszlo, Z.I., Rajkumar, S., Demir, T., Hindley, N., Lamont, D.J., Lehmann, J., Seidel, M., Sommer, D., Franz-Wachtel, M., Barletta, F., Heumos, S., Czemmel, S., Kabashi, E.,  Ludolph, A., Boeckers, T.M., Henstridge, C.M.* and Catanese, A*. (2023) Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS. Acta Neuropathologica. 146(3):451-475. * co-senior author
• Henstridge, C.M., Pickett, E.K. and Spires-Jones, T.L. (2016) Synaptic pathology: a shared mechanism of neurological disease. Ageing Research Reviews. 28: 72-84.
• Henstridge, C.M., Sideris, D.I., Carroll, E., Rotariu, S., Salomonsson, S., Tzioras, M., McKenzie, C.A., Smith, C., von Arnim, C.A.F., Ludolph, A.C., Lulé, D., Leighton, D., Warner, J., Cleary, E., Newton, J., Swingler, R., Chandran, S., Gillingwater, T.H., Abrahams, S. and Spires-Jones, T.L. (2018) Synapse loss in the prefrontal cortex is associated with cognitive decline in amyotrophic lateral sclerosis. Acta Neuropathologica, 135(2):213-226
• Laszlo, Z.I., Hindley, N., Sanchez Avila, A., Kline, R.A., Eaton, S.L., Lamont, D.J., Smith, C., Spires-Jones, T.L., Wishart, T.M. and Henstridge, C.M. (2022) Synaptic proteomics reveal distinct molecular signatures of cognitive change and C9ORF72 repeat expansion in the human ALS cortex. Acta Neuropathologica Comms. 10, Article number: 156
• Sanchez Avila, A. and Henstridge, C.M. (2022) Array tomography: 15 years of synaptic analysis. Neuronal Signalling. 23;6(3) NS20220013

BMSc Neuropharmacology and Behaviour - module co-lead

BMSc Neuropharmacology and Behaviour - lecturer

MSc Science and Healthcare Communications - lecturer

MSc Applied Neuroscience – lecturer and tutor

BBSE Neuroscience - lecturer

Medical students, 1st year SSC1 module - tutor