[18F]THK-5351 PET Patterns in Patients With Alzheimer’s Disease and Negative Amyloid PET Findings

Minyoung Oh, Jungsu S. Oh, Seung Jun Oh, Sang Ju Lee, Jee Hoon Roh, Woo Ram Kim, Ha Eun Seo, Jae Myeong Kang, Sang Won Seo, Jae Hong Lee, Duk L. Na, Young Noh, Jae Seung Kim

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1 Citation (Scopus)


Background and Purpose Alzheimer’s disease (AD) does not always mean amyloid positivity. [18F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [18F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings. Methods We performed 3.0-T magnetic resonance imaging, [18F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [18F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern. Results The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [18F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread (n=10) and extratemporal spread (n=13). Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [18F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p=0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p=0.006) but not in the intratemporal spread group (-0.5±2.8, p=0.916). The diagnosis remained as AD (n=5, 50%) or changed to other diagnoses (n=5, 50%) in the intratemporal group, whereas it remained as AD (n=8, 61.5%) or changed to frontotemporal dementia (n=4, 30.8%) and other diagnoses (n=1, 7.7%) in the extratemporal spread group. Conclusions Approximately 70% of the patients with amyloid-negative AD showed abnormal [18F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern.

Original languageEnglish
Pages (from-to)437-446
Number of pages10
JournalJournal of Clinical Neurology (Korea)
Issue number4
Publication statusPublished - 2022 Jul
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 Korean Neurological Association.


  • Alzheimer’s disease
  • [F]THK-5351
  • amyloid
  • neuropsychological test
  • positron-emission tomography

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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