{
  "abstract": "Background\n\nSilver staining continues to serve as a critical technique for histological detection of pathological deposits, especially in the context of Alzheimer's disease (AD). In clinical research, paraffin-embedded sections are often stored for extended periods, and tissues may remain in formaldehyde for prolonged durations, both of which can lead to false-negative results. The objective of this study was to systematically evaluate whether heat-induced retrieval can enhance the efficacy and sensitivity of classical silver staining in these suboptimally preserved brain tissues.Methods\n\nThis study investigated the impact of heat-induced retrieval methods on silver staining efficacy in brain tissue. Three types of samples were examined: standard FFPE sections, tissues immersed in formaldehyde for 48 months, and paraffin‑embedded sections (initially fixed for 48 h in formalin, sections coated with paraffin and stored on slides) stored for seven years. Retrieval methods were performed using citrate-citric acid buffer, Tris-EDTA buffer, or proteinase K. Silver staining was conducted using three classical methods: Bielschowsky, periodic acid-methenamine silver (PAM), and Gallyas; untreated sections were used as controls.Results\n\nResults showed that both citrate-citric acid and Tris-EDTA significantly increased the signal-to-noise ratio of senile plaques in Bielschowsky staining. This improvement facilitated better the detection of amyloid plaque details and density, with Tris-EDTA yielding higher sensitivity in long-stored paraffin sections. Proteinase K digestion did not enhance Bielschowsky staining results. None of the retrieval methods improved signal-to-noise ratio for senile plaques or neurofibrillary tangles with PAM or Gallyas.Conclusions\n\nThese findings indicate that heat-induced retrieval methods with citrate or Tris-EDTA buffer, enabling more efficient silver ion reduction at specific targets in Bielschowsky. This work provides an experimental basis for optimizing silver staining protocols, which helps enhance diagnostic accuracy in neuropathological studies of AD and related disorders.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anatomy, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, 230032, P. R. China.",
    "Department of Pharmacy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, P. R. China.",
    "School of Pharmacy, Anhui Medical University, Hefei, Anhui, 230032, P. R. China.",
    "Institute of Brain Science, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, P. R. China.",
    "Department of Pharmacy, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, P. R. China. yfy347812@fy.ahmu.edu.cn.",
    "School of Pharmacy, Anhui Medical University, Hefei, Anhui, 230032, P. R. China. yfy347812@fy.ahmu.edu.cn.",
    "Department of Anatomy, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, 230032, P. R. China. cwwang@ahmu.edu.cn.",
    "Institute of Brain Science, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, P. R. China. cwwang@ahmu.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhi-Yi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shan-Shan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuai-Deng Wang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Kun Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Wen-Hui Yi"
    },
    {
      "affs": [
        0
      ],
      "name": "Zi-Wei Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Jiang-Ning Zhou"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Xin-Meng Wang"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Chen-Wei Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bxpp0ksz8368x.bib",
  "cited_by": 0,
  "doi": "10.1186/s13000-026-01799-3",
  "fulltext_url": "https://europepmc.org/articles/PMC13726164",
  "id": "bxpp0ksz8368x",
  "issns": [
    "1746-1596"
  ],
  "landing_url": "https://europepmc.org/article/MED/42968096",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2737|Alzheimer's disease research and treatments"
    ]
  ],
  "openalex": "W7171486684",
  "pdf_url": "https://europepmc.org/articles/PMC13726164?pdf=render",
  "pmcid": "PMC13726164",
  "pmid": "42968096",
  "published": "2026-07-29",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/bxpp0ksz8368x.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:54Z",
      "native_id": "MED:42968096",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42968096"
    },
    {
      "first_seen": "2026-11-05T12:22:34Z",
      "native_id": "PMC13726164",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13000-026-01799-3"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Alzheimer's disease research and treatments",
      "subfield": "physiology"
    }
  ],
  "title": "Impact of heat-induced retrieval methods on silver staining for detecting senile plaques of Alzheimer's disease in human brain tissue sections.",
  "title_text": "Impact of heat-induced retrieval methods on silver staining for detecting senile plaques of Alzheimer's disease in human brain tissue sections.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:11Z",
  "url": "https://research.draconitic.com/paper/bxpp0ksz8368x",
  "venue": "Diagnostic pathology",
  "versions": []
}