Rinsho Shinkeigaku (Clinical Neurology)

The 50th Annual Meeting of the Japanese Society of Neurology

In-vivo imaging for pursuing molecular cascades in the pathogenesis of neurodegenerative diseases

Makoto Higuchi, M.D.

Molecular Imaging Center, National Institute of Radiological Sciences

Nonclinical and clinical evidences have supported the view that accumulations of neurotoxic amyloid components initiate chain reactions of molecular and cellular pathologies, eventually leading to neuronal death and symptomatic onsets of neurodegenerative diseases. As this amyloid-triggered cascade is virtually composed of bidirectional causalities between upstream and downstream events, it is of critical significance to monitor all key processes, including amyloidosis, neuroinflammation, disrupted calcium homeostasis and impaired neurotransmissions, in living brains toward therapeutic regulations of the entire cascade. Positron emission tomography (PET) offers quantitative mapping of these alterations with the aid of multiple classes of radioprobes. Comparative PET assays of humans and animal models in conjunction with cognitive, biochemical and histopathological assessments have revealed toxic subspecies of amyloid β peptide, tau proteins and microglia detectable by specific molecular probes. Dysregulated neurotransmissions are also capturable by PET techniques, while it should be noted that the accessibility of binding components to exogenous radioligands does not simply reflect their amounts but also is affected by their translocation, posttranslational modifications and interaction with endogenous ligands and other molecules. Clarification of these changes in target elements brings mechanistic insights into the molecular etiology of neuropsychiatric disorders.
Full Text of this Article in Japanese PDF (445K)

(CLINICA NEUROL, 49: 929|932, 2009)
key words: Alzheimer's disease, translational research, aging, positron emission tomography, genetically engineered animal models

(Received: 22-May-09)