ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Assessing Aβ-independent effects of Module 42 on immune function in vitro.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionA deep multi-omic analysis of post mortem human brains has identified a new co-expression protein network - Module 42 (M42), strongly corelated with Alzheimer's disease (AD) pathology. M42 comprises 32 transmembrane and extracellular matrix (ECM)-associated proteins, including the amyloid precursor protein (APP) and apolipoprotein E (apoE), and its members have been implicated in amyloid beta (Aβ) pathology. We systematically evaluated the Aβ-independent effects of M42 on immune function in vitro.
methodsRecombinant M42 proteins were expressed and purified. Their effects on phagocytosis, intracellular signaling, and cell viability were assessed in human induced pluripotent stem cell-derived macrophages.
resultsTreatment with Midkine (MDK) reduced phagocytosis, while treatment with the ectodomain of Transmembrane protein with EGF-like and two follistatin-like domains 2 (TMEFF2) had the opposite effect. Both proteins promoted intracellular Ca DISCUSSION: Our results suggest an additional role for M42 in AD via regulating immune functions. HIGHLIGHTS: We tested M42 proteins for their effects on immune functions in vitro. Five proteins altered phagocytosis, and seven altered Ca
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