Both brains and genes linked to Alzheimer’s disease

Australian research, presented at the Alzheimer’s Association International Conference this week, has highlighted the links between a person’s brain chemistry, genes and their risk of developing Alzheimer’s disease (AD).

Professor Paul Maruff, Chief Science Officer at cognition testing company Cogstate, explained that the findings have come from the ongoing Australian Imaging Biomarkers and Lifestyle (AIBL) study. The largest of its kind in the world, the study started in 2006 and involves more than 1000 people aged over 60 years.

“The aim of this study is to find the earliest indications of subtle neurodegenerative disease,” Professor Maruff said. “By then pairing observations about behaviour with data from biomarkers or imaging, we can determine the extent to which these early behavioural or cognitive changes arise from an Alzheimer’s disease process.”

One of the risk factors identified was an elevated level of beta amyloid in the brain, long suspected to play a role in the disease due to its substantial presence in the post-mortems of Alzheimer’s patients. Recent advances in neuroimaging and cerebral spinal fluid analysis mean scientists can now detect beta amyloid in people while they are alive - thus, its relationship with cognitive and behavioural changes can be better understood.

The second risk factor relates to brain-derived neurotrophic factor (BDNF) - a gene which encodes for the BDNF protein and is necessary for learning and memory. If the gene variation BDNF Val66Met is present alongside high beta amyloid levels, this signals, “those at highest risk and patients in whom cognitive deterioration was more rapid”, said Professor Maruff.

“This is important because it can help to identify those with the most to gain from early drug and perhaps even behavioural intervention designed to prevent AD,” he said.

“This research will also help to identify those older people who have mild cognitive impairment (MCI) but who have a low risk of AD, meaning their impairment may have other causes such as depression or stress which are more readily treatable.”

The research comprised four studies, with data collected through Cogstate’s cognition test battery. Professor Maruff said of the battery, “it does not suffer from practice effects, it is fast to administer and it does not cause individuals to become fatigued or demotivated with repeated assessment”. These characteristics increased the sensitivity of the study “to amyloid-related cognitive change in otherwise healthy older people and in people with MCI”.

Professor Maruff was a co-author on all four papers. Their key findings include:

• Among healthy older people, and people who meet clinical criteria for MCI, high brain amyloid levels indicate that AD-related neuro-degeneration has begun and that memory will now decline at a constant rate.
• In healthy older people with abnormally high brain amyloid levels who also carry the BDNF Val66Met gene, memory and other aspects of cognition will decline faster than in those who do not carry this variant.
• Older people diagnosed with MCI, and who have normal brain amyloid levels, do not show decline in memory over time and therefore their cognitive impairment may be due to other more readily treatable causes.
• The sensitivity of Cogstate’s cognition testing was confirmed as a “useful tool for the identification of AD-related memory impairment” in clinical settings.

Around 30% of Australians aged over 60 years are known to have high brain amyloid levels, according to Professor Maruff. Among this group, around one in three will also carry the BDNF Val66Met gene variation.

But the research findings means that help is on the way. As we understand more about how Alzheimer’s develops, it can be detected in people faster and new therapies can be developed for treatment.