Brain cells that support neurons change most as we
get older, suggesting a new focus for dementia
research.
The main changes in our brains as we get older are in the brain
cells with a supporting role, called glial cells, British
scientists have found.
The surprising finding in a study by researchers at the
Francis Crick Institute and UCL (University College London) is
published in the journal Cell Reports.
The researchers also found that the greatest changes in
glial cells as we age are in the brain regions most often damaged
by neurodegenerative disease, like Alzheimer's and
Parkinson's.
The discovery suggests the interactions between glial
cells and neuronal cells, the nerve cells active in mental function
and forming memories, should be a focus of future dementia,
Alzheimer's and Parkinson's disease research.
Jernej Ule, a Group Leader at the Francis Crick Institute
and a professor at UCL's Institute of Neurology, said: "Sadly,
getting older affects the brain just as much as other parts of the
body. To understand more, we looked at how different types of brain
cells change over time in healthy individuals. Knowing more about
healthy ageing in different parts of the brain can also give us an
insight into the damage caused by diseases like Parkinson's or
Alzheimer's.
"It was a surprise to find that the genes specific for
glial cells in our brains showed the most dramatic changes in
expression as we age," he added. "Typically we have concentrated on
neurons, as they are the cells involved in brain processing and
memories. We may now need to change our focus."
The scientists analysed brain tissue samples from 480
healthy people who were between 16 and 106 years old when they
died. They looked at patterns of gene expression in neuron and
glial cells in 10 different brain regions (see image
above).
"Sadly, getting older
affects the brain just as much as other parts of the body."
Jernej Ule
They used dedicated computational analyses- involving data
mining and machine learning approaches - to examine the cell
populations present in images scanned from stained brain sections.
Each image would typically include hundreds of thousands of brain
cells and is scanned in high resolution.
Most of the samples were provided by a UK brain bank, the
Sudden Death MRC brain bank based in Edinburgh, which stores post
mortem brain tissue donated for research. This large resource,
confirmed by samples from other brain banks, allowed the team to
tell the story of how healthy human brains age.
The team's findings and the new resource of data this
research has generated provide an important foundation for future
studies that apply a similar approach to learn more about
neurodegenerative diseases.
Dr Rickie Patani of UCL, whose team is shortly moving into
the new Francis Crick Institute building, said: "Integrating
traditional gene expression techniques with powerful computational
and imaging methods has given us a new insight into the way the
brain changes as it ages. It's not neurons that change most but the
supportive glial cells. This suggests we need to focus on the
relationship between these cells, if we are to learn more about
dementia and other devastating neurodegenerative
diseases."
First author Dr Lilach Soreq, of the Francis Crick
Institute and UCL, said: "We looked at brain tissue from healthy
people aged 16 to 106 years old. Our computational approaches
allowed us to analyse a huge dataset. It revealed that the glial
cells that surround and insulate neurons appear to have something
of an identity crisis as we age. At younger ages, there are
distinct patterns of gene expression seen among glial cells in
different parts of the brain. But these patterns reduce as we
age."
The research was funded by the European Research Council,
a Marie Curie fellowship, the Alzheimer's Society, the Francis
Crick Institute (which receives its core funding from the Medical
Research Council, Cancer Research UK, Wellcome, UCL, Imperial
College London and King's College London), the Medical Research
Council and the US National Institutes of Health.