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

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.

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.

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.

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.