Immune-cell composition in the human hippocampus appears to change sharply during midlife, according to an NIH-supported molecular atlas of neurologically healthy postmortem brain tissue.
Researchers examined hippocampal samples from 40 donors ages 20 to 95. The hippocampus supports learning and memory and is affected early in several age-related brain disorders.
The team combined single-cell gene-expression data with measurements of three-dimensional genome organization and epigenetic regulation. That approach allowed investigators to distinguish cell types and examine how their control systems changed with age.
Resident immune cells called microglia declined most noticeably from roughly ages 50 to 75. During the same period, inflammatory and peripheral-like immune cells became more prominent in the samples.
Researchers also reported deterioration in cells associated with the blood-brain barrier and disruption in genome architecture. These molecular patterns identify associations with aging, not proof that a specific change caused disease.
The tissue came from donors without known neurological disease, which helps describe healthy aging but limits direct conclusions about Alzheimer's disease, Parkinson's disease or other diagnoses.
Postmortem studies provide a detailed snapshot but cannot track the same person's brain through time. Differences among donors, tissue quality and the 40-sample size also constrain how precisely the timing can be generalized.
The investigators say future work should test whether the midlife transition can be modified and whether it helps explain vulnerability to later disease. The current study does not establish a diagnostic test or treatment.
NIH reported support from grants R01AG067153, R01AG082127 and 1U01DA052769. The peer-reviewed findings appeared in Science with DOI 10.1126/science.adt8307.