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Alzheimer’s-linked DNA marks recur in independent brain samples

Chemical marks on brain DNA were associated with Alzheimer’s pathology in a large postmortem study, and some findings recurred in independent samples. The peer-reviewed investigation examined methylation alongside amyloid and tau. It also connected a methylation score with APOE-linked genetic risk, while leaving the timing and causal role of the changes unresolved.

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Two physically separate preserved postmortem prefrontal brain-tissue sample trays.

DNA marks accompany brain pathology

A peer-reviewed Nature Aging study linked methylation, chemical marks on DNA rather than changes in its sequence, with Alzheimer’s pathology in postmortem human brains. The investigation also examined how those marks relate to the genetic risk associated with APOE.[1], [2]

Prefrontal tissue came from 1,250 participants in five cohorts at the Rush Alzheimer’s Disease Center, a brain ageing research centre. Researchers assessed pathological diagnosis, amyloid accumulation and tau tangles. After quality control, 875,741 autosomal sites remained in the analysis, with age, sex, cell composition and experimental variation accounted for.[1]

Independent samples repeat some of the signals

The initial analysis identified 107 associated methylation sites. Of these, 38 replicated in the same direction in 139 samples from the Netherlands Brain Bank, a brain tissue repository: 62 Alzheimer’s cases and 77 controls. Gene-expression measurements from participants’ brain cells also found differences involving 39 genes across cell types.[1]

APOE association includes a methylation component

Statistical mediation attributed 8.6 per cent of the APOE ε4–pathology association to a methylation score, with a confidence interval of 4.3–14.6 per cent. The postmortem cross-sectional design cannot determine whether the marks preceded disease or followed it. The work measured brain-tissue associations rather than testing a treatment or a blood-based early diagnosis.[1]

References

  1. News sourceNature AgingPostmortem brains reveal DNA methylation associated with Alzheimer’s pathology↩1↩2↩3↩4
  2. News sourceScienmagChemical Tags on Brain DNA Reveal How Alzheimer’s Risk Genes Do Their Damage↩
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