CJCADR Public Dementia Forum part 1: QBI research

On February 19, the Clem Jones Centre for Ageing Dementia Research at QBI hosted a public forum on dementia, covering a wide range of topics from current research and clinical therapeutics to approaches to care and the societal impact that dementias have. The impetus was to bring together people from all aspects of dementia research and care for an exchange of ideas, and to provide an overview that would help members of the public understand the range of approaches being taken in fighting dementia. In part 1 here, I relay some of the science presented at the forum. In part 2, I cover aspects of dementia care and treatment as covered by the forum’s speakers.

Victoria Beedle, CEO of Alzheimer’s Australia QLD, opened the Forum and discussed the personal and societal impacts of the disease. Dementia carries with it a certain stigma that can lead to feelings of isolation in those affected – nearly 60% of AD patients reported feeling as though people avoided contact with them. To help address this, Alzheimer’s Australia is trialling the development of a dementia-friendly community in Bribie Island. In this community, transport and physical environments are tailored to assist in reducing confusion, the ability to live at home with access to carers is prioritised, and patients are offered opportunities for community involvement. Together, these measures should minimise the sense of isolation and enhance the feeling of independence amongst dementia sufferers. Victoria presented an overview of Alzheimer’s Australia QLD 2015 programs and activities; printed material is available from their State Office. Tel. 07 3895 8200. National Dementia Helpline 1800 100 500.

A number of QBI researchers gave brief accounts of their research. CJCADR director Professor Jürgen Götz began with a general overview of dementias, highlighting the crucial involvement of insoluble protein aggregates in disease pathology. In Alzheimer’s Disease (AD), which accounts for 50–70 per cent of all dementias, the two proteins responsible appear to be amyloid beta (Aβ) and tau, which form aggregates outside and inside of the cell, respectively. Research into potential therapeutics therefore focusses on limiting protein aggregation. An approach showing some promise is immunotherapy, in which antibodies are developed to target and remove or break down aggregates of Aβ or tau. Although a number of clinical trials on anti-Aβ antibodies have been conducted, the majority show only limited efficacy, a generalisation that also holds for anti-tau antibodies. Improvements in antibodies are underway, focussing on improving the access they have to the protein aggregates and decreasing the side effects they produce.

Dr Jana Vukovic spoke next on how newly born neurons may guard against dementia. For years, dogma held that the neurons you were born with were the neurons you had for life, but it’s now clear that in a process termed neurogenesis, two parts of the brain – the hippocampus and olfactory bulb – produce new neurons throughout life, although this process slows with age. Given that newly born neurons have been implicated in learning and memory, the possibility of artificially enhancing neurogenesis to combat dementia is appealing. Dr Vukovic showed that exercise in mice promotes the birth of new neurons, and that this process depends on microglia, cells in the brain responsible for immune defence. Furthermore, the ability of microglia to support neurogenesis was enhanced by providing them with a particular protein, the chemokine CX3CL1.

Dr Victor Anggono spoke of events leading to a key event in early neurodegeneration, the loss of synapses, which can occur following exposure to Aβ. Synapses can be lost because they are no longer sufficiently active, and one mechanism that can cause this reduction in communication is the removal of neurotransmitter receptors, which are responsible for initiating signalling in the postsynaptic neuron. Dr Anggono has shown previously that receptors can be tagged for removal by a chemical modification called ubiquitination. Finding a way to interfere with such receptor tagging looms as a potential means to prevent synapse loss and neurodegeneration.

Moving away from studies in mice, Associate Professor Elizabeth Coulson showed that neuroimaging in humans could be used to predict Alzheimer’s pathology. Patients with Alzheimer’s Disease exhibit a massive 75% decrease in the number of cholinergic neurons in the basal forebrain. Cholinergic neurons are so-called because they release the neurotransmitter acetylcholine, and a number of currently approved therapeutics for AD target the acetylcholine system, as do several late-phase clinical trial drugs. Associate Professor Coulson showed that the volume of the basal forebrain (where the majority of the brain’s cholinergic neurons reside) correlated with the degree of cognitive impairment. Furthermore, a similar correlation held even in pre-symptomatic patients, meaning that basal forebrain volume could serve as a biomarker to predict subsequent cognitive impairment.

The Clem Jones Centre for Ageing Dementia Research opened only two years ago, on February 28, 2013, after an initial philanthropic contribution from the Clem Jones Trust was leveraged to attract further state and federal funding. The research presented at this forum is testament to the substantial contributions already being made to dementia research by QBI scientists, in a variety of distinct yet complementary basic research fields.