Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 3 min ago
Peer-reviewedCC BY-NC-ND 4.0European Journal of Nuclear Medicine and Molecular Imaging

APOE4-dependent cholinergic/dopaminergic contributions to clinical symptoms across Alzheimer’s disease spectrum: A retrospective observational study

  • Sungwoo Kang1
  • Seun Jeon2
  • Donggeon Lee2
  • Hanbi Lee2
  • Su-Hee Jeon2
  • Minsun Choi2
  • Young-gun Lee3
  • Na-Young Shin4
  • Mijin Yun5
  • Byoung Seok Ye6
6 affiliations
  1. 1Department of Neurology, Hanyang University College of Medicine, Seoul, 04763 Republic of Korea
  2. 2Metabolism-Dementia Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea
  3. 3Department of Neurology, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, 10380 Republic of Korea
  4. 4Department of Radiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea
  5. 5Department of Nuclear Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea
  6. 6Department of Neurology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722 Republic of Korea
Read full textPDFDOICite

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.

Methods: 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.

Results: 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.

Conclusion: 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.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08165-x.

Related

  1. The human LRRK2-R1441G mutation drives age-dependent oxidative stress and mitochondrial dysfunction in dopaminergic neurons
    Yuanxin Chen, Lianteng Zhi, Shiquan Cui +3
    Molecular NeurodegenerationPeer-reviewedCC BYFull text1 citedNeurologyDOAJ
  2. Mechanisms involved in the sex-dependent dopaminergic neurodegeneration induced by MDMA in a mouse model of adolescent drug exposure
    Giulia Costa, Laura Rullo, Vera Piera Leoni +12
    Frontiers in PharmacologyPeer-reviewedCC BY 4.0Full textPharmacology & toxicologyFrontiersCrossrefDOAJ
  3. Genetic and non-genetic contributions to early spontaneous miscarriage in women with PCOS undergoing PGT-A and single euploid blastocyst transfer: a retrospective cohort study
    Zhiqin Bu, Xiaofei Ge, Jing Sun +1
    BMC Pregnancy and ChildbirthPeer-reviewedCC BY-NC-ND 4.0Full textObstetrics, gynaecology & paediatricsPMC
  4. Characterization of Medication-Related Errors and Prioritization of Patient-Safety Interventions in Hospital Care: A Retrospective Observational Study
    C. R. Kokate
    medRxivPreprintAll rights reservedFull textEpidemiology & public healthmedRxiv
  5. Low-intensity extracorporeal shockwave therapy for chronic prostatitis/chronic pelvic pain syndrome: a retrospective single-center observational study in Japan
    Translational andrology and urologyPeer-reviewedCC BY-NC-NDFull textGeneral medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{kang2026apoe4dependent,
  title = {{APOE4-dependent cholinergic/dopaminergic contributions to clinical symptoms across Alzheimer’s disease spectrum: A retrospective observational study}},
  author = {Sungwoo Kang and Seun Jeon and Donggeon Lee and Hanbi Lee and Su-Hee Jeon and Minsun Choi and Young-gun Lee and Na-Young Shin and Mijin Yun and Byoung Seok Ye},
  journal = {European Journal of Nuclear Medicine and Molecular Imaging},
  year = {2026},
  month = sep,
  doi = {10.1007/s00259-026-08165-x},
  url = {https://doi.org/10.1007/s00259-026-08165-x},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - APOE4-dependent cholinergic/dopaminergic contributions to clinical symptoms across Alzheimer’s disease spectrum: A retrospective observational study
AU  - Sungwoo Kang
AU  - Seun Jeon
AU  - Donggeon Lee
AU  - Hanbi Lee
AU  - Su-Hee Jeon
AU  - Minsun Choi
AU  - Young-gun Lee
AU  - Na-Young Shin
AU  - Mijin Yun
AU  - Byoung Seok Ye
PY  - 2026
DA  - 2026/09/09
JO  - European Journal of Nuclear Medicine and Molecular Imaging
DO  - 10.1007/s00259-026-08165-x
UR  - https://doi.org/10.1007/s00259-026-08165-x
AB  - 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.  Methods: 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.  Results: 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.  Conclusion: 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.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08165-x.
SN  - 1619-7070
SN  - 1619-7089
ER  -