Advances in the field of frontotemporal dementia over the past 15 years have been breath-taking in genetic, molecular and clinical arenas. A corresponding expansion of the International Conference on Frontotemporal Dementia from a handful to 550 participants now provides a forum where clinicians and researchers from vastly different backgrounds come together and discuss their work. So I set off for Manchester with an open mind and came away with a degree of optimism about the future.

Clinical considerations

Carers were a particular focus of the conference. The burden that carers undergo was highlighted in two presentations, including psychological techniques to help carers cope better with the stresses of inappropriate behaviour and apathy. A parallel meeting for carers was well attended. Selina Wray (Alzheimer’s Research Trust Research Fellow at the Department of Molecular Neuroscience, University College, London) received an award in recognition of her engagement with carers, and told me “It was great to see such a large turnout of around 100 carers, many of whom had travelled long distances to be at the meeting (including one couple from Switzerland). I was impressed by their enthusiasm to find out more about FTD research and it was a privilege to talk to them about our own ongoing work and to hear their stories and experiences in return.”

Although FTD was in the conference title, related tau-associated diseases and motor neurone disease were mentioned often. The murky world of clinicopathological correlation was a theme for a number of clinical talks. In addition to known associations such as semantic dementia and TDP-43 accumulation, Keith Josephs and Jennifer Whitwell presented evidence from the Mayo clinic that the recently described syndrome of progressive apraxia of speech reliably predicts tau aggregation.1 However, the link to pathology is still uncertain in most syndromes, in particular behavioural variant FTD.

Neuropsychology presentations added some depth to the debates around clinical features, but did not have a large impact on discussions of diagnosis or prediction of pathology.

Imaging has emerged as a useful intermediate phenotype between the molecular and clinical. DTI scans in pathologically confirmed cases, presented by Corey McMillan from the University of Pennsylvania, were able to differentiate tau pathology from TDP-43. He used a data-driven factor analysis that took advantage of the white matter degeneration characterising tau-related neurodegeneration.2

Disease modification

Understanding mechanisms of disease and identifying targets for drugs is a key part of many biochemical and cellular research programmes. Karen Duff’s (Taub Institute for Alzheimer’s Disease Research, Columbia University) talk on how tau protein may propagate between cells and be taken up by mass endocytosis stood out as a carefully considered look at the emerging concept of direct protein spread contributing to pathological changes.3 However, questions remain around why some neurons are more susceptible to pathology, the role of glial cells and whether this mechanism is sufficient in itself to cause disease.

Disease modifying treatments were often mentioned, usually as a long-distant aim, but with two notable exceptions. The much anticipated results of a phase 2/3 trial of Davunetide (Allon Therapeutics) in Progressive Supranuclear Palsy are due in early 2013, a microtubule stabiliser showing encouraging functional improvements in mouse models and administered via a nasal spray. Seglin, a compound at a much earlier stage of development was discovered by Summit PLC to inhibit O-GlcNAcase (OGA) and prevent the conversion of tau oligomers to aggregates.

A cautious message from Jada Lewis (McKnight Brain Institute, University of Florida) highlighted that despite encouraging efforts in animal models, the recently discovered genetic defects have a long way to go before they are realistically replicated in mice or other animals.


Genetics permeated virtually every session of the meeting, particularly the recently discovered C9ORF72 found in an astounding one third of familial FTD and around 5% of sporadic disease.4 The enthusiasm of finding this mutation has clearly not worn off yet, particularly on Bryan Traynor who introduced the FTD and Motor Neurone Disease session. He animatedly talked about his own ‘Eureka moment’ on finding the mutation, but highlighted that international collaborations have been vital and will continue to be vital in making advances in what remains a relatively rare disease.

A lively debate discussed whether to spend more money on genetics in FTD, with two heavy-weights in the field taking a light-hearted but passionate approach. Chris Shaw argued there is still much genetic variability in disease to discover, and John Hardy proposed we channel existing knowledge towards mechanistic understanding and drug discovery.


The standard of science was high, although research and clinical work in diverse disciplines did feel like floating islands still gradually drifting towards each other. Bridges are beginning to form, but there is some way to go in achieving a ‘grand theory’ of how genetic changes influence molecular and cellular processes to result in diverse pathologies and explain the clinical syndromes of FTD and its related disorders. In the meantime people with FTD and their carers benefit from what we learn about the clinical syndromes.

At the welcoming reception Ian Jacobs (Dean of the Faculty of Medical/Human Sciences at Manchester University) pointed out the camaraderie he saw among conference delegates. Established scientists and clinicians rubbed shoulders and talked to younger researchers in a relaxed atmosphere. Those relationships will be vital if the multiple calls for collaboration and data pooling are to succeed. It seems the field of FTD is in good shape to take on the many challenges still to face.


1.      Josephs KA, Duffy JR, Strand EA, Machulda MM, Senjem ML, Master AV, et al. Characterizing a neurodegenerative syndrome: primary progressive apraxia of speech. Brain. 2012 135(Pt 5):1522–36. Available from:

2.      McMillan C, Brun C, Siddiqui S, Churgin M. White matter imaging contributes to the multimodal diagnosis of frontotemporal lobar degeneration. Neurology. 2012 78:1761–8. Available from:

3.      Liu L, Drouet V, Wu J, Witter M, Small S, Clelland C, et al. Trans-Synaptic Spread of Tau Pathology In Vivo. PloS one. 2012 7(2):1–9. Available from:

4.      Hodges JR. Familial frontotemporal dementia and amyotrophic lateral sclerosis associated with the C9ORF72 hexanucleotide repeat. Brain. 2012 135(3):652–5.  Available from:

The next International Conference will be held in October 2014 in Vancouver, Canada