Prefrontal cortex transcriptomes distinguish Alzheimers disease from asymptomatic amyloid pathology, neuropeptide loss, immune-complement activation and glial remodelling

In dorsolateral prefrontal cortex, symptomatic Alzheimer’s disease shows 496 differentially expressed genes versus amyloid-positive tau-negative ageing, including neuropeptide loss and complement–immune activation.

• Why it matters: The transcriptional differences that distinguish symptomatic AD from amyloid-positive, tau-negative pathology ageing and from pathology-free ageing are still unclear in association cortex.
• What they did: The authors re-analysed bulk RNA-seq from DLPFC of 15 donors (87 runs aggregated), using DESeq2 for differential expression and GO/KEGG over-representation, with exploratory APOE and TREM2 p.Arg47His contrasts.
• The result: AD downregulated neuropeptide/hormone signalling (e.g., VGF, VIP, CRH) and upregulated interferon-γ response and classical complement (C1QA/B/C), while also inducing gliogenesis and oligodendrocyte/myelination programmes and P2RX7 (log2FC = 1.46).

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