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Alzheimer's disease
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What is Alzheimer's disease?

Alzheimer's disease (AD) is the leading cause of neurodegenerative dementia symptomatically characterized by impairments of memory and other cognitive functions and pathologically defined by the presence of hallmark lesions in form of senile plaques and neurofibrillary tangles. Despite its notable negative impacts on societies with growing elderly population, the causal mechanisms of AD are yet to be clarified. The diagnosis of AD is clinically made by applying diagnostic criteria based on behavioral and neuropsychological assessments with the aid of conventional neuroimaging (CT, MRI, etc.) and laboratory tests, and becomes definite only by a postmortem autopsy. The morbid duration of AD is estimated as being between 5 and 20 years, and accumulation of amyloid fibrils forming senile plaques and neurofibrillary tangles is known to precede its symptomatic onset by decades. Accordingly, detection of amyloid deposition in living subjects provides the prospect of innovative techniques for diagnosis of AD at a presymptomatic stage.

 
Characteristic pathologies in Alzheimer's disease
Senile plaques
Senile plaques
Neurofibrillary tangles
Neurofibrillary tangles
 

Our research projects on AD are primarily aimed at establishing imaging biomarkers useful for early diagnosis and emerging disease-modifying treatments of this devastating illness, by gaining new insights into molecular pathogenesis of AD and related neurodegenerative disorders from human subjects and animal models of these pathological conditions.

Clinical research:
PET studies for patients with mild cognitive impairment (MCI) and AD are performed to elucidate the time course of amyloid deposition and its association with cognitive decline in the continuum from normal aging to AD.

 
PET images of β amyloid deposition in aged humans
Normal aged
Normal aged
(No deposition)
MCI
MCI
(slight deposition)
AD
AD
(remarkable deposition)
 

Animal research:
By investigation of transgenic (TG) mice recapitulating aggregation of amyloid fibrils using in vivo small animal-dedicated imaging system, followed by in vitro histochemical and biochemical assays of their brain tissues, we characterize imaging agents newly developed for visualization of amyloid and associated pathophysiological events in AD brains. This methodology is also employed in proving mechanistic concepts of potential therapeutic interventions capable of counteracting amyloid-triggered neurodegenerative processes.

 
PET images of β amyloid deposition in mice
Wile-typed aged
Wile-typed aged
(No deposition)
TG
TG
(remarkable deposition)
Laterally treated TG
Laterally treated TG
(collateral reduction)
Maeda J et al, J Neurosci, 2007
 
 
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