The utility of positron emission tomography in cardiac amyloidosis.

Cardiac amyloidosis, characterized by progressive restrictive cardiomyopathy, presents unusual diagnostic challenges. Conventional cardiac scintigraphy has shown limited utility in the quantification of disease burden and serial follow-up of cardiac amyloidosis. The advent of specialized positron emission tomography with specific amyloid-binding radiotracers has the potential to change currently employed diagnostic algorithms for the imaging of cardiac amyloidosis. This review aims to discuss the diagnostic utility of amyloid-binding radiotracers, including Pittsburg compound B, florbetapir, florbetapan, and sodium fluoride. These tracers have promising potential for the early detection of the particular type of cardiac amyloidosis, pursuing relevant medical intervention, assessing amyloid burden, monitoring treatment response, and overall prognostication.

Amyloid deposition and CBF patterns predict conversion of mild cognitive impairment to dementia.

Mild cognitive impairment (MCI) can include the transition from a normal state to dementia. To explore biomarkers for the development of dementia, we performed an 18-month follow-up study in 28 patients with amnestic MCI. Amyloid deposition was examined using PiB PET, and cerebral blood flow (CBF) was examined using SPECT. Cognitive function was periodically assessed. The rate of conversion to dementia was higher in the PiB-positive/equivocal group (74%) than in the PiB-negative group (33%) (p = 0.041). Perfusion SPECT was performed in 16 patients. MCI patients with an AD-characteristic pattern of reduced CBF had a higher PiB-positive/equivocal rate (82%) than those with a non-AD pattern (20%) (p = 0.018), and patients with an AD pattern had a higher conversion rate (82%) than those with a non-AD pattern (40%) (p = 0.094). Clinically, all PiB-positive converters were diagnosed as having Alzheimer's disease (AD), whereas PiB-negative converters were thought to have some form of dementia other than AD. Amyloid PET is useful for predicting conversion to AD in MCI patients. A pattern analysis of perfusion SPECT findings might also be helpful for predicting conversion to AD, but with a lower specificity.

Ligand-based molecular MRI: O-17 JJVCPE amyloid imaging in transgenic mice.

BACKGROUND: Development of molecular MR imaging (MRI) similar to PET imaging using contrast agents such as gadolinium as probe have been inherently hampered by incompatibility between potential probe (charged molecules) and membrane permeability. Nevertheless, considering the inherent spatial resolution limit for PET of 700µ, the superior microscopic resolution of MRI of 4 µ presents a strong incentive for research into ligand-based molecular MRI. METHODS: (17) O exhibits JJ vicinal coupling with a covalently bound proton in a hydroxyl group. This (17) O coupled proton can be ionized in water solution and interexchange with other water protons. This property can be utilized as "probe" in T2-weighted imaging and developed into ligand-based molecular MRI. We examined ß-amyloid distribution in human APP overexpressed transgenic mice in vivo following injection of (17) O labeled Pittsburg compound B ((17) O-PiB). RESULTS: JJVCPE imaging successfully imaged (17) O-PiB, unequivocally establishing that (17) O JJVCPE imaging can be developed into PET-like molecular MRI in clinical medicine. CONCLUSIONS: The study represents the first successful ligand-based molecular MRI in vivo. This is also the first in vivo amyloid imaging using MRI. High-resolution molecular MRI with high specificity under clinical settings, such as in vivo microscopic imaging of senile plaque, is a foreseeable aim.

Synaptic changes in Alzheimer's disease and its models.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by a progressive loss of cognition and the presence of two hallmark lesions, senile plaques (SP) and neurofibrillary tangles (NFT), which result from the accumulation and deposition of the ß-amyloid peptide (Aß) and the aggregation of hyperphosphorylated tau protein, respectively. Initially, it was thought that Aß fibrils, which make up SP, were the root cause of the massive neurodegeneration usual found in AD brains. Over time, the longstanding emphasis on fibrillar Aß deposits and neuronal death slowly gave way to a new paradigm involving soluble oligomeric forms of Aß, which play a prominent role in triggering the cognitive deficits by specifically targeting synapses and disrupting synaptic signaling pathways. While this paradigm is widely accepted today in the AD field, the molecular details have not been fully elucidated. In this review, we address some of the important evidence, which has led to the Aß oligomer-centric hypothesis as well as some of the key findings concerning the effects of Aß oligomers on synapses at a morphological and functional level. Understanding how Aß oligomers target synapses provides an important framework for ongoing AD research, which can lead to the development of successful therapeutic strategies designed to alter or perhaps reverse the course of the disease.