Immune Cells Change as the Human Brain Ages
Scientists have identified major immune and genetic changes in the human brain beginning during midlife.
The findings could help researchers understand why ageing significantly increases the risk of Alzheimer’s disease and other forms of dementia.
The study focused on the hippocampus, a brain region essential for learning and memory.
Researchers found that its immune-cell environment underwent substantial changes between approximately 50 and 75 years of age.
The brain’s resident immune cells, known as microglia, gradually declined during this period.
They were replaced by cells showing stronger inflammatory characteristics and molecular features resembling immune cells found in the blood.
Researchers said this transition could contribute to chronic brain inflammation associated with neurodegenerative conditions.
However, the study did not prove that these changes directly cause Alzheimer’s disease or predict which individuals will develop dementia.
Researchers Examined More Than One Million Brain Cells
The research team analysed postmortem hippocampal tissue from 40 neurologically healthy adults.
The donors ranged from 20 to 95 years old.
Scientists from the University of California San Diego, New York Genome Center and University of California Irvine participated in the research.
They used advanced single-cell technologies to examine gene activity, epigenetic changes and the three-dimensional organisation of DNA.
This approach allowed scientists to study ageing-related changes across individual brain-cell types.
The results showed that brain ageing may not occur through a slow and uniform decline.
Instead, several immune, vascular and neuronal systems appear to undergo coordinated changes during midlife and later adulthood.
Researchers also found deterioration in cells that support the blood-brain barrier.
This protective barrier helps prevent potentially harmful substances in the bloodstream from entering brain tissue.
The study further identified widespread disruption in the three-dimensional structure of the genome across several types of brain cells.
Scientists said these structural changes were closely connected with altered gene regulation and cellular identity.
Findings Could Guide Future Dementia Research
Ageing is the largest known risk factor for dementia, but scientists still do not fully understand how it increases vulnerability to disease.
The newly identified immune-cell transition may offer an important clue.
Microglia normally protect the brain, remove damaged material and help maintain a stable environment around nerve cells.
When these cells decline or change their behaviour, harmful material may accumulate and inflammatory activity may increase.
Researchers now plan to investigate what causes resident microglia to disappear and whether their replacement contributes directly to Alzheimer’s disease.
Future studies may also examine whether protecting microglia or the blood-brain barrier could help preserve brain function.
The findings could eventually support the development of treatments targeting changes that begin years before serious memory problems appear.
The researchers stressed that the results should not be treated as a test for dementia.
The study examined donated brain tissue after death and did not follow living participants to determine who later developed cognitive decline.
Further research involving larger and more diverse populations will be needed.
The findings were published in the journal Science as part of the National Institutes of Health’s 4D Nucleome research programme.
