New PET scan can detect earliest signs of Alzheimer's disease

Scientists have developed a new positron emission tomography (PET) imaging technique that can detect one of the earliest signs of Alzheimer's and help in timely diagnosis of the disease.

The technique involves an agent, a radiotracer named 18F-SMBT-1, that can detect the presence of overexpressed monoamine oxidase-B (MAO-B) enzyme in cognitively unimpaired individuals with high beta amyloid (Aβ), which is one of the earliest signs of Alzheimer's.

This allows for a better understanding of the role of inflammation in the disease, thereby, enabling more accurate staging and prognosis at earlier stages.

The 18F-SMBT-1 agent is highly selective for MAO-B enzyme and as a result has an increased binding to reactive astrocytes, which are cells that overexpress MAO-B.

Brain inflammation that accompanies Alzheimer’s disease involves reactive astrocytes.

"This increased binding suggests that 18F-SMBT-1 can potentially be used as a surrogate marker to detect reactive astrogliosis in Alzheimer’s disease," said Victor Villemagne, lead author of the study, from the University of Pittsburgh, US.

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Study participants included three clinical groups: 57 cognitively unimpaired controls, 12 subjects meeting criteria for mild cognitive impairment (MCI), and eight subjects meeting criteria for Alzheimer’s disease.

Participants in the study, published in Journal of Nuclear Medicine, were classified based on their Aβ status (either as Aβ+ or Aβ negative).

No significant differences in 18F-SMBT-1 binding were found among Aβ negative participants in the control and MCI groups, the study said.

The scientists found that in the Aβ+ subjects with Alzheimer’s disease, 18F-SMBT-1 binding was significantly higher.

Most importantly, 18F-SMBT-1 binding was significantly higher in the Aβ+ control group as compared to Aβ negative control group.

"It is of note that the brain regions where we saw this higher 18F-SMBT-1 binding in the control group are regions known for early Aβ deposition. This suggests that reactive astrocytes are associated with early Aβ deposition at the preclinical stages of Alzheimer's disease and likely play a role over clinical progression," said Villemagne.

The study aimed to characterise 18F-SMBT-1 binding to reactive astrocytes across the Alzheimer’s disease continuum.

Participants underwent several types of imaging, including 18F-SMBT-1 PET, Aβ PET, tau PET, and MRI. Images were normalised and statistical analyses conducted to assess 18F-SMBT-1 binding in relation to Aβ and tau pathology burden.

18F-SMBT-1 was found to be highly correlated with Aβ burden, and much less with tau burden, the researchers said.

"Implementation of 18F-SMBT-1 will clarify the role of reactive astrogliosis in neurodegenerative conditions, not just Alzheimer's disease and its potential independent and/or synergistic effects on pathology, neurodegeneration, cognition, and disease progression.

"This has the potential to define and refine the diagnostic, staging and prognostic roles of reactive astrogliosis in these conditions," said Villemagne.