Implementation of [: first-hand experience in Thailand18: first-hand experience in ThailandF]-labeled amyloid brain PET imaging biomarker in the diagnosis of Alzheimer’s disease: first-hand experience in Thailand

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Alzheimer’s disease (AD) is the main cause of dementia in the elderly worldwide 1. This progressive and irreversible neurodegenerative disorder is characterized by gradual memory loss and cognitive decline, which leads to severely impaired activities of daily living 2 and significant burdens not only on the patients and their families but also on the socioeconomic status and healthcare 3. Clinical diagnosis and conventional structural imaging have limitations because of their unreliability and insensitivity in the diagnosis of AD. Examination of brain tissue by biopsy or autopsy has been the best method to establish a definite diagnosis of AD 4 in the presence of pathological hallmarks: extracellular amyloid β (Aβ) plaque and intracellular neurofibrillary tangles mainly composed of hyperphosphorylated tau protein aggregrated, together with evidences of neurodegeneration including widespread cellular degeneration, reactive gliosis, diffuse synaptic, and neuronal loss 5–7. However, with the development of new diagnostic modalities, we can now use noninvasive in-vivo techniques to detect the pathology of AD to identify the population at risk before developing clinical symptoms and predict progression of the disease. These techniques also raise the possibility of therapeutic development and response assessment of the disease-specific therapy 8. Recently, several novel imaging biomarker-based criteria for early diagnosis of AD have been proposed that would enable preventive and therapeutic interventions during the preclinical stage of AD 9–11.
Assessment of Aβ plaque deposition in the brain using PET imaging is a well-validated biomarker for the diagnosis of AD at the preclinical and prodomal stage. Furthermore, PET imaging of amyloid deposition in the brain can be used for the differential diagnosis of AD versus mild cognitive impairment. Several studies have shown that patients who are amyloid positive on PET were more likely to progress to clinically symptomatic AD during the follow-up period 12–14. However, the presence of amyloid deposition does not necessarily correlate with pathologic neurodegeneration, disease severity, and cognitive decline 15–16. Moreover, it should be noted that cerebral amyloid (Aβ) deposits can also be found in other types of dementia, including dementia with Lewy bodies 17, posterior cortical atrophy 18, cortical amyloid angiopathy 19, and Parkinson’s disease with dementia 20. The absence of amyloid (Aβ) deposits can be expected in frontotemporal lobe dementia 17, Creutzfeldt–Jakob disease 21, and most of cognitively intact Parkinson disease 22. The latter findings may be useful in the differential diagnosis of the cause for atypical dementia. It is also known that Aβ plaques can be detected in up to 25–35% of cognitively normal aging patients and that the detection rate increases with age 23–24. However, the association between amyloid burden in the brain and poor memory performance in healthy elderly patients supports the hypothesis of preclinical stage of AD, which has not yet manifested with clinical symptoms, rather than just a normal finding in an aging population 8.
To date, five commonly used PET tracers have been developed for the detection of cerebral Aβ deposition (in chronological order): (a) [11C]-Pittsburg compound B ([11C]-PiB), (b) [18F]-florbetapir (Amyvid; Avid Radiopharmaceuticals, Philadelphia, Pensylvania, USA and Eli Lilly and Company, Indianapolis, Indiana, USA), (c) [18F]-flutemetamol (Vizamyl; GE Healthcare, Milwaukee, Wisconsin, USA), (d) [18F]-florbetaben (Neuraceq; Piramal Imaging, Berlin, Germany), and (e) [18F]-NAV4694 (formerly [18F]-AZD4694; AstraZeneca, Cambridge, England). The characteristics of these PET tracers and their interpreting criteria for positive amyloid scan are summarized in Table 1. Several tracers are also being developed and currently undergoing clinical trials.
Among these tracers, [11C]-PiB is the first tracer used to detect Aβ with high affinity and selectivity for fibrillar Aβ in the plaque 8.

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