Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET.

Objective: Multimodal imaging techniques have furthered our understanding of how different aspects of Alzheimer's disease (AD) pathology relate to one another. Diffusion tensor imaging (DTI) measures such as mean diffusivity (MD) may be a surrogate measure of the changes in gray matter structure associated with AD. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has been used to quantify synaptic loss, which is the major pathological correlate of cognitive impairment in AD.

In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET.

Introduction: Synaptic loss is a robust and consistent pathology in Alzheimer's disease (AD) and the major structural correlate of cognitive impairment. Positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) has emerged as a promising biomarker of synaptic density.

Methods: We measured SV2A binding in 34 participants with early AD and 19 cognitively normal (CN) participants using [ C]UCB-J PET and a cerebellar reference region for calculation of the distribution volume ratio.

A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease.

Introduction: Despite significant progress, a disease-modifying therapy for Alzheimer's disease (AD) has not yet been developed. Recent findings implicate soluble oligomeric amyloid beta as the most relevant protein conformation in AD pathogenesis. We recently described a signaling cascade whereby oligomeric amyloid beta binds to cellular prion protein on the neuronal cell surface, activating intracellular Fyn kinase to mediate synaptotoxicity.

Volumetry of amygdala and hippocampus and memory performance in Alzheimer's disease.

Magnetic resonance imaging (MRI) is showing increased utility in examining medial temporal lobe atrophy and its relationship to memory performance in Alzheimer's disease (AD). We studied 56 AD patients and 42 older healthy subjects with neuropsychological assessment and MRI. Hippocampal and amygdaloid volumes (normalized to intracranial volume) were contrasted between AD patients and healthy controls and correlated with neuropsychological performance.

Apolipoprotein E epsilon4 is associated with atrophy of the amygdala in Alzheimer's disease.

Although the ApoE epsilon4 allele is well-established as the most important genetic risk factor for Alzheimer's disease (AD), the effects of this allele on regional brain atrophy in AD patients remain controversial. We performed MRI-based volumetric measurements of the hippocampus and amygdala (normalized to intracranial volume) in 32 epsilon4+ AD patients, 23 epsilon4- AD patients, and 42 cognitively normal elderly control subjects. Analysis of covariance revealed that amygdaloid volume was significantly smaller (19.