Alzheimer's disease

25 July 2016

Brain Research New Zealand – Rangahau Roro Aotearoa have multiple labs and multi-disciplinary teams working across four Universities. They are investigating treatments, interventions and preventions for Alzheimer’s disease.

Through the hard work and collaborative effort of many individuals, these groups have been fortunate to gain multi-million dollar funding from the Health Research Council and Neurological Foundation of New Zealand in order to expand our Alzheimer’s disease research capabilities.

BRNZ_Alzheimers Parkinsons

Alzheimer's, Parkinson's... and the inner ear

Balance-related organs in our inner ear, called the "vestibular system", have been associated with higher cognitive functions like learning and memory.

Discovering more about these intriguing links has proved tough, however, simply because it has been difficult for scientists to navigate through the inner ear's bony labyrinth.

A new rat-based study focused on a surgical approach that effectively activates the individual sensors and nerves located in the inner ear could pave the way for an incredible new type of prostheses.

Such tiny devices - similar to cochlear implants to treat hearing loss - could potentially enhance memory and improve balance for Alzheimer's and Parkinson's disease patients and ageing populations.

Professor Paul Smith, who has been researching the concept with fellow Brain Research New Zealand principal investigator Dr Yiwen Zheng as part of a global collaboration, says the first "artificial vestibular systems" had been implanted in the past few years.

They worked by sensing head movement and electrically stimulating the nerves that normally supply nerves to the vestibular sensory receptors to provide the brain with the self-motion information it needed.

Over the past decade, it had become apparent this information - the result of a sensory system more than 500 million years old - was important for the "spatial memory" that tells us where we've been.

"We use vision and other sensory information as well, but the vestibular system is much older in evolutionary terms and therefore is a pivotal source of information for orientation in the world," Smith says.

Previously it was impossible to electrically stimulate specific parts of the system in small research animals like rats but Smith and his colleagues overcame the hurdle.

"We developed a surgical approach to selectively electrically stimulate all of the different receptor groups of the vestibular system in the rat - making it possible to investigate the effects of artificial vestibular stimulation on the brain and better understand the full consequences of vestibular implants for human patients."

Originally published in the NZ Herald 'Brain Detectives: 10 Amazing Kiwi Insights'.  

Reference 

Anatomy and surgical approach of rat's vestibular sensors and nerves. Hitier M1, Sato G2, Zhang YF3, Zheng Y3, Besnard S4, Smith PF3, Curthoys IS5. J Neurosci Methods. 2016 Sep 1;270:1-8. doi: 10.1016/j.jneumeth.2016.05.013. Epub 2016 May 19.

BRNZ_memory

The protein that can boost memory

A certain type of protein may have the power to enhance memory.

Professor Warren Tate, who has just reported the discovery he made with Otago University colleague Professor Cliff Abraham in the journal Neurobiology of Learning and Memory, unlocked this secret by focusing not on the "villain" in Alzheimer's disease, but on a hidden and distantly-related hero.

The protein they developed in the lab, called "secreted amyloid precursor protein-alpha", was impressively able to restore memory mechanism in aged animals - indicating it could be a useful therapeutic target in Alzheimer's disease.

Much of the focus has been on a protein fragment known as beta-amyloid, regarded as the disease's causative agent, but Tate and Abraham looked at another piece of the same larger protein it was part of.

"Although what we are looking at is not as intensely studied as beta-amyloid, our view is that it's important because it's neuro-protective, and therefore might protect against neurological damage and ageing," Tate says.

"So we are looking at what you might call the good guy, rather than the bad guy."

Using the brains of aged rats, the researchers simulated what might happen in a human brain if the protein was supplied.

"We've done quite a lot of work on this and we've found that if you inhibit mammalian memory mechanisms and then provide the protein we've produced in our lab, it will actually reverse the effects, both in terms of electrophysiology - that is, measuring memory - and also behavioural learning.

"So we know it's important - and we know that it has restorative properties."

Watch this space.

Originally published in the NZ Herald 'Brain Detectives: 10 Amazing Kiwi Insights'.  

Reference

 Secreted amyloid precursor protein-alpha can restore novel object location memory and hippocampal LTP in aged rats.  Xiong M1, Jones OD1, Peppercorn K2, Ohline SM1, Tate WP2, Abraham WC3.

BRNZ_Alzheimers2

Painting a picture of Alzheimer's disease

In Alzheimer's disease, cells in the part of the brain that control memory and learning, called the hippocampus, slowly start dying.

Yet researchers still don't really know why these certain cells are targeted.

Searching for an answer, Auckland University researcher Lakshini Mendis and Associate Professor Maurice Curtis and Professor Richard Faull turned to lipids, which envelope the cell machinery and serve as the basic building blocks of living cells.

To compare differences in lipids in Alzheimer's and normal brain tissue, they drew on a relatively new imaging technique that allowed them to see exactly where in the hippocampus these different lipids were distributed.

"It enabled us to find out which regions of the brain affected by Alzheimer's disease were high in particular categories of lipids and in which regions they were low," Curtis says.

"This could be important because if a person has an abnormal array of lipids, they might have abnormal proteins and this leads to dysfunction in the hippocampus where memories are made.

"We also know lipids are really important, for instance, in stabilising cell membranes and allowing cells to produce and use neurotransmitters properly - this is something that allows us to see exactly where in the brain things are going wrong."

The team were eventually able to identify specific types of lipids that were much more abundant in a normal brain than in one affected by Alzheimer's.

The molecular picture they created offered a better insight into the role of lipids - and a was a valuable contribution to global Alzheimer's research efforts.

Originally published in the NZ Herald 'Brain Detectives: 10 Amazing Kiwi Insights'.  

Reference

Mendis, L. H. S., Grey, A. C., Faull, R. L. M. and Curtis, M. A. (2016), Hippocampal lipid differences in Alzheimer's disease: a human brain study using matrix-assisted laser desorption/ionization-imaging mass spectrometryBrain and Behavior, 0(0), e00517, doi: 10.1002/brb3.517

BRNZ_dementia

Better blood flow could slow the cognitive decline riddle  

It's a question that has long baffled neuroscientists: why do some people show less cognitive decline than others as they age?

In a study led by Otago University researcher Dr Liana Machado, young and older adults were asked to complete cognitive tests while the study team measured blood-flow patterns in their brains.

As expected, older adults performed worse than young adults on the cognitive tests.

Yet the older adults also showed different blood-flow patterns, indicating they used more brain areas than the young adults while completing the cognitive tests - especially as the tests got harder.

Importantly, in the older adults, using more brain areas was associated with a better test performance, indicating the extra brain areas helped boost cognitive performance.

Now the researchers have established a relationship between blood flow and cognitive performance, Machado said it could be possible to help those not performing as well.

"Basically, if we can get the older adults who are having cognitive difficulties to increase their blood flow in the brain - particularly in the frontal lobe, which is where we saw the higher levels - then maybe we can help them perform better."

This could be done either through low levels of electrical brain stimulation, targeting the frontal lobe, or simply by encouraging them to engage in more physical activity, such as brisk walking, to improve their blood flow.

 Originally published in the NZ Herald 'Brain Detectives: 10 Amazing Kiwi Insights'.  

Reference

 Cognitive Difficulty Intensifies Age-related Changes in Anterior Frontal Hemodynamics: Novel Evidence from Near-infrared Spectroscopy. Bierre KL, Lucas SJ, Guiney H, Cotter JD, Machado L.

BRNZ_Alzheimers1

The powerhouse protein to turn against Alzheimer's disease

Scientists have found what could be another big puzzle piece to tackling Alzheimer's - a mighty and intriguing protein called PSA-NCAM.

It effectively allows brain cells to remodel their shape and their connections with other cells and, importantly, it has also been linked to the disease.

Using adult human brain tissue from the Neurological Foundation Human Brain Bank, Auckland University PhD student Helen Murray and her colleagues revealed PSA-NCAM was produced by mature brain cells in specific regions of the adult human brain. 

Its widespread distribution highlighted the incredible capacity of the brain to change and adapt throughout adult life, says the study's senior author, Associate Professor Maurice Curtis.

"This was interesting work that demonstrated many brain regions are geared up for plasticity."

Associate Professor Maurice Curtis of The University of Auckland 

Capable of rearranging itself in response to external stimuli, like a person's changing world, the PSA-NCAM allows brain circuits to be modified, enabling the addition of new memories throughout life.

The team compared the amount of PSA-NCAM in normal, Alzheimer's and Parkinson's disease brains, finding the protein decreased only in a specific region of the Alzheimer's disease brain involved in memory, and that this drop was linked to levels of toxic tau proteins.

Pinpointing this particular region, called the "entorhinal cortex", was crucial.

"It tells us there's one circuit in the brain that's really involved in Alzheimer's disease - and it's one that seems to be deficient in this key plasticity marker," Curtis says.

"That's really quite good in a way, because it gives us a target to focus on, something we can potentially manipulate."

Originally published in the NZ Herald 'Brain Detectives: 10 Amazing Kiwi Insights'.  

Reference

Distribution of PSA-NCAM in normal, Alzheimer's and Parkinson's disease human brain. Murray HC1, Low VF2, Swanson ME3, Dieriks BV4, Turner C5, Faull RL6, Curtis MA7.

 

Margaret dudly

There is a critical lack of research into Maori and dementia

Clinical psychologist Dr Margaret Dudley (Te Rarawa, Te Aupōuri and Ngāti Kahu) is a BRNZ Principal Investigator conducting research at the University of Auckland. She has been awarded 2016 Health Research Council funding to undertake a 48 month project entitled: 'A Māori approach to the assessment and management of dementia' worth over a million dollars. 

Research summary 

As kaumatua experience increasing life expectancy, the prevalence of dementia for Maori is also predicted to increase. In 2011, 1,928 Maori were estimated to have had dementia which is expected to increase to 4,493 by 2026.

However, there is a critical lack of research about Maori and dementia. This research aims to improve existing approaches to the assessment and management of dementia for Maori by providing one that is informed by matauranga Maori.

The methodology will interface Kaupapa Maori research methodology with Western scientific processes. Hui with kaumatua ropu and whanau who suffer from dementia will be held and information from those sources will inform a Kaupapa Maori Theory of dementia, and the development of a tool that is responsive to Maori needs and an effective clinical measure to screen for dementia.

This research addresses a need for indigenous research that better meets the needs of Maori suffering from dementia.

The dementia prevention research clinics

Potential blood test for Alzheimer’s disease

An exciting discovery by Brain Research New Zealand researchers could pave the way for Alzheimer's to be diagnosed by a simple blood test.

The discovery was made as part of a $4.6 million Health Research Council of New Zealand programme grant, directed by Prof Cliff Abraham, looking into markers and therapeutic targets for Alzheimer's and other dementias, which now affect more than 50,000 New Zealanders.

“The team's ultimate goal was to develop a blood test that could spot the disease early, before people showed any clinical signs”, said Professor Abraham.

The researchers have discovered a promising new marker among a small number of molecules, within a larger class of molecules called microRNA.

The marker molecules, found both in the human brain and blood, were “exceptionally good” at detecting Alzheimer's, the researchers said.

Further research is needed to confirm and further clarify aspects of the earlier testing work, and, if the results can be confirmed and further clarified, it is understood that a blood test could become available about five years after that.

The HRC funding has been crucial in gaining these promising diagnostic results. Further results will not be available until later this year, and important groundwork still has to be done before a clinical trial for a therapy is possible.

The proposed new test could have many advantages, including being quick and easy to administer, relatively inexpensive and readily available. 

BRNZ ALZ month

In September 2016, Brain Research New Zealand will embark upon a nation-wide series of community public forums.

These offer the Alzheimer’s disease and dementia community with the opportunity to make direct contact with the researchers and to gain insights into the exciting and promising research which is happening nation-wide by Brain Research New Zealand’s researchers located at the universities of Otago, Auckland, Canterbury and AUT.

Dozens of teams of BRNZ neuroscientists and clinicians are tackling Alzheimer’s disease, dementia and mild cognitive impairment from every angle and ensuring that the entire spectrum of research is being carried out from bench to bedside. 

Flyer for Alzheimer's Awareness Month 2016 

Alzheimer's Manawatu: Professor Louise Nicholson

Alzheimer's Napier: Dr Andrea Kwakowsky 

Alzheimer's Nelson: Professor Ngaire Kerse 

Alzheimer's Northland: Helen Murray & Lakshini Mendis

Alzheimer's Taranaki: Dr Phil Wood.

Alzheimer's Tauranga: Associate Professor Maurice Curtis 

Alzheimer's Waikato: Karen Smith 

Alzheimer's Whakatane: Associate Professor Maurice Curtis 

Alzheimer's Wairarapa: Dr Jian Guan

The talks cover different aspects of disease and disorder prevention, intervention and amelioration for:  

  • Alzheimer's disease
  • Dementia & mild cognitive impairment
  • Parkinson's disease
  • Huntington's disease
  • Stroke

For community groups, BRNZ can offer 

  1. The latest information about research into Alzheimer’s disease, dementia, stroke, Parkinson’s disease and Huntington’s disease.
  2. Opportunities to ask questions and provide feedback to some of New Zealand's best neuroscientists and clinicians regarding your experience as a carer, patient or family member.
  3. Opportunities to extend your support network. 

To arrange a speaker for your next community event, contact us marcomms@brnz.ac.nz