{
  "abstract": "Purpose: Clinical heterogeneity in Alzheimer’s disease (AD) may reflect differential involvement of neurotransmitter systems, but whether the associations of cholinergic and dopaminergic imaging biomarkers with cognitive and neuropsychiatric symptoms differ according to apolipoprotein E ε4 (APOE4) status remains unclear.\n\nMethods: We studied 387 patients across the amyloid-confirmed AD spectrum. Patients were stratified by APOE4 status into 205 carriers and 182 non-carriers. Basal forebrain volume (BFV), striatal dopamine transporter uptake (DAT), and regional brain perfusion were examined in relation to cognitive performance and neuropsychiatric inventory scores.\n\nResults: APOE4 carriers showed lower BFV than non-carriers, whereas APOE4 non-carriers showed lower DAT. In APOE4 carriers, lower BFV was associated with memory dysfunction and AD-typical temporoparietal hypoperfusion; the BFV-memory association was attenuated after inclusion of posterior cingulate perfusion. Lower BFV was also associated with several neuropsychiatric symptoms, including hallucinations, delusions, anxiety, apathy, aberrant motor behavior, and appetite changes, with direct associations remaining for hallucinations, delusions, and apathy after accounting for regional perfusion. In APOE4 non-carriers, lower DAT was associated with poorer performance across widespread cognitive domains and with hallucinations, delusions, and anxiety. These DAT associations largely persisted even after adjustment for regional perfusion.\n\nConclusion: APOE4 status was associated with differences in the clinical and brain perfusion correlates of cholinergic and dopaminergic degeneration in AD. APOE4 carriers showed a BFV-dominant pattern linked to AD-typical perfusion changes and memory dysfunction, whereas non-carriers showed a DAT-dominant pattern with largely perfusion-independent associations with cognitive and neuropsychiatric manifestations.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08165-x.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Hanyang University College of Medicine, Seoul, 04763 Republic of Korea",
    "Metabolism-Dementia Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea",
    "Department of Neurology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, 10380 Republic of Korea",
    "Department of Radiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea",
    "Department of Nuclear Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea",
    "Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sungwoo Kang"
    },
    {
      "affs": [
        1
      ],
      "name": "Seun Jeon"
    },
    {
      "affs": [
        1
      ],
      "name": "Donggeon Lee"
    },
    {
      "affs": [
        1
      ],
      "name": "Hanbi Lee"
    },
    {
      "affs": [
        1
      ],
      "name": "Su-Hee Jeon"
    },
    {
      "affs": [
        1
      ],
      "name": "Minsun Choi"
    },
    {
      "affs": [
        2
      ],
      "name": "Young-gun Lee"
    },
    {
      "affs": [
        3
      ],
      "name": "Na-Young Shin"
    },
    {
      "affs": [
        4
      ],
      "name": "Mijin Yun"
    },
    {
      "affs": [
        5
      ],
      "name": "Byoung Seok Ye",
      "orcid": "0000-0003-0187-8440"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2jyyb4dqvjw52.bib",
  "cited_by": 0,
  "doi": "10.1007/s00259-026-08165-x",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13727942/",
  "id": "2jyyb4dqvjw52",
  "issns": [
    "1619-7070",
    "1619-7089"
  ],
  "landing_url": "https://doi.org/10.1007/s00259-026-08165-x",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
    [
      "openalex",
      "2738|Dementia and Cognitive Impairment Research"
    ]
  ],
  "openalex": "W7212038584",
  "pdf_url": "https://link.springer.com/content/pdf/10.1007/s00259-026-08165-x.pdf",
  "pmcid": "PMC13727942",
  "pmid": "42714593",
  "published": "2026-09-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2jyyb4dqvjw52.ris",
  "sources": [
    {
      "first_seen": "2026-11-06T12:23:43Z",
      "native_id": "PMC13727942",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00259-026-08165-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2738|Dementia and Cognitive Impairment Research",
      "subfield": "psychiatry"
    }
  ],
  "title": "APOE4-dependent cholinergic/dopaminergic contributions to clinical symptoms across Alzheimer’s disease spectrum: A retrospective observational study",
  "title_text": "APOE4-dependent cholinergic/dopaminergic contributions to clinical symptoms across Alzheimer’s disease spectrum: A retrospective observational study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:21:02Z",
  "url": "https://research.draconitic.com/paper/2jyyb4dqvjw52",
  "venue": "European Journal of Nuclear Medicine and Molecular Imaging",
  "versions": []
}