The antimicrobial protein, CAP37, is upregulated in pyramidal neurons during Alzheimer's disease.

Amanda J Brock, Anne Kasus-Jacobi, Megan Lerner, Sreemathi Logan, Adekunle M Adesina, H Anne Pereira

Histochemistry and cell biology 2015 Oct

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Inflammation is a well-defined factor in Alzheimer's disease (AD). There is a strong need to identify the molecules contributing to neuroinflammation so that therapies can be designed to prevent immune-mediated neurotoxicity. The cationic antimicrobial protein of 37 kDa (CAP37) is an inflammatory mediator constitutively expressed in neutrophils (PMNs). In addition to antibiotic activity, CAP37 exerts immunomodulatory effects on microglia. We hypothesize that CAP37 mediates the neuroinflammation associated with AD. However, PMNs are not customarily associated with the pathology of AD. This study was therefore designed to identify non-neutrophilic source(s) of CAP37 in brains of AD patients. Brain tissues from patients and age-matched controls were analyzed for CAP37 expression using immunohistochemistry (IHC). To determine factors that induce CAP37 in AD, HCN-1A primary human neurons were treated with tumor necrosis factor-alpha (TNF-α) or amyloid β1-40 (Aβ) and analyzed by IHC. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to confirm CAP37 expression in neurons and brain tissues. IHC revealed CAP37 in cortical neurons in temporal and parietal lobes as well as CA3 and CA4 hippocampal neurons in patients with AD. CAP37 was found in more neurons in AD patients compared with age-matched controls. qRT-PCR and Western blotting showed an increase in CAP37 transcript and protein in the AD temporal lobe, a brain region that is highly impacted in AD. qRT-PCR observations confirmed CAP37 expression in neurons. TNF-α and Aβ increased neuronal expression of CAP37. These findings support our hypothesis that neuronal CAP37 may modulate the neuroinflammatory response in AD.

Citation

Amanda J Brock, Anne Kasus-Jacobi, Megan Lerner, Sreemathi Logan, Adekunle M Adesina, H Anne Pereira. The antimicrobial protein, CAP37, is upregulated in pyramidal neurons during Alzheimer's disease. Histochemistry and cell biology. 2015 Oct;144(4):293-308