{
  "abstract": "The progressive aggregation of amyloid beta (Aβ) monomers into oligomers is a critical factor in Alzheimer's disease (AD) pathogenesis. Although mutated forms of Aβ have been shown to display altered aggregation dynamics, the specific effects of deamidated Aβ on microglial function remain understudied. Our research group previously found that the deamidated variant Aβ-42-N27D modified Aβ aggregation, reduced neurotoxicity, and reduced microglial reactivity, but the impact of Aβ-42 side chain deamidation in general on such parameters remained unclear. Here, we expanded on our prior work by investigating how two site-specific Aβ-42 mutations (Q15E & N27D), where neutral amide side chains are replaced with negatively charged carboxylic acids, affect aggregation and microglial immune response using a mouse microglial cell line. Size exclusion chromatography, Thioflavin T fluorescence, circular dichroism, and dynamic light scattering revealed that Aβ-42-Q15E and Aβ-42-N27D exhibit reduced aggregation compared to Aβ-42 wild type (WT). Multiplexed analysis of 8 microglial cytokines secreted into the culture medium revealed that Aβ-42-Q15E and Aβ-42-N27D decrease the expression of inflammatory cytokines such as IL-6, IP-10, and MIP-1α relative to Aβ-42-WT. Immunocytochemistry revealed that Aβ-42-Q15E and Aβ-42-N27D decrease CD68 expression and intracellular Aβ labeling relative to Aβ-42-WT. These findings demonstrate that deamidation significantly alters Aβ-42 aggregation and microglial activation, suggesting structural modifications to Aβ-42 modulate inflammatory signaling in AD. This work provides a foundation for future studies on Aβ-42 post-translational modifications as potential therapeutic targets in AD.",
  "abstract_shown": true,
  "affiliations": [
    "George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia30332, United States.",
    "School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia30332, United States.",
    "Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia30332, United States.",
    "School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia30332, United States.",
    "Department of Chemistry and Biochemistry, University of California Santa Cruz, Santa Cruz, California95064, United States.",
    "T-NeuroDx, Albuquerque, New Mexico87123, United States.",
    "StemVax Therapeutics, a NovAccess Global Company, Chagrin Falls, Ohio44023, United States.",
    "World Brain Mapping Foundation, Society for Brain Mapping & Therapeutics, Pacific Palisades, California90272-3668, United States.",
    "Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia30332, United States."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Martin N Griffin"
    },
    {
      "affs": [
        1
      ],
      "name": "Daniel M Dinakarapandian",
      "orcid": "0009-0000-0081-3958"
    },
    {
      "affs": [
        2
      ],
      "name": "Chenxing Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Pranay Ramaswamy"
    },
    {
      "affs": [
        2
      ],
      "name": "Sia J Saheba"
    },
    {
      "affs": [
        2
      ],
      "name": "Janie Lee"
    },
    {
      "affs": [
        1
      ],
      "name": "Tarunya Rao Sudarshan"
    },
    {
      "affs": [
        4
      ],
      "name": "Maria Sajimon",
      "orcid": "0000-0002-6753-6841"
    },
    {
      "affs": [
        4,
        5,
        6,
        7
      ],
      "name": "Christopher J Wheeler"
    },
    {
      "affs": [
        4
      ],
      "name": "Jevgenij A Raskatov",
      "orcid": "0000-0002-0082-9113"
    },
    {
      "affs": [
        1,
        8
      ],
      "name": "Anant K Paravastu",
      "orcid": "0000-0001-7183-1942"
    },
    {
      "affs": [
        0,
        2,
        8
      ],
      "name": "Levi B Wood",
      "orcid": "0000-0002-4248-0888"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fe6c184msb6as.bib",
  "cited_by": 0,
  "doi": "10.1021/acschemneuro.6c00024",
  "fulltext_url": "https://europepmc.org/articles/PMC13693379",
  "id": "fe6c184msb6as",
  "issns": [
    "1948-7193"
  ],
  "landing_url": "https://europepmc.org/article/MED/42904641",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W4415487392",
  "pdf_url": "https://europepmc.org/articles/PMC13693379?pdf=render",
  "pmcid": "PMC13693379",
  "pmid": "42904641",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fe6c184msb6as.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42904641",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42904641"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Aβ-42 Side Chain Deamidation at Q15 or N27 Modulates Protein Aggregation and Alters Microglial Cytokines and CD68.",
  "title_text": "Aβ-42 Side Chain Deamidation at Q15 or N27 Modulates Protein Aggregation and Alters Microglial Cytokines and CD68.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/fe6c184msb6as",
  "venue": "ACS chemical neuroscience",
  "versions": []
}