Lance A. Johnson

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Gangliosides, sialic acid-bearing glycosphingolipids, are highly enriched in the vertebrate nervous system. Anti-ganglioside antibodies are associated with various human neuropathies, although the pathogenicity of these antibodies remains unproven. Testing the pathogenic role of anti-ganglioside antibodies will be facilitated by developing high-affinity(More)
Oxidative stress (OS) and reactive oxygen species (ROS) play a modulatory role in synaptic plasticity and signaling pathways. Mitochondria (MT), a major source of ROS because of their involvement in energy metabolism, are important for brain function. MT-generated ROS are proposed to be responsible for a significant proportion of OS and are associated with(More)
Relatively little is known about early irradiation effects on hippocampal function in wild-type mice. In this study, the effects of (56)Fe irradiation on hippocampal function were assessed starting 2 weeks after whole-body irradiation. Compared to sham irradiation, radiation impaired novel object recognition in female and male C57BL/6J wild-type mice. There(More)
Apolipoprotein E (apoE) is an essential component of lipoprotein particles in both the brain and periphery, and exists in three isoforms in the human population: E2, E3, and E4. ApoE has numerous, well-established roles in neurobiology. Most notably, E4 is associated with earlier onset and increased risk of Alzheimer’s disease (AD). Although possession of(More)
There are well-known genetic background effects on atherosclerosis susceptibility in mice. To study the basis of these effects, we have generated the apolipoprotein E-null mutation in mouse embryonic stem cells of 129/SvEv origin, maintained it in the inbred strain (129-apoE), and compared these mice with those previously made in strain 129/Ola and(More)
Given the multiple differences between mice and men, it was once thought that mice could not be used to model atherosclerosis, principally a human disease. Apolipoprotein E-deficient (apoEKO) mice have convincingly changed this view, and the ability to model human-like plaques in these mice has provided scientists a platform to study multiple facets of(More)
Human apolipoprotein E (apoE) exists in three isoforms: apoE2, apoE3 and apoE4. APOE ε4 is a major genetic risk factor for cardiovascular disease (CVD) and Alzheimer's disease (AD). ApoE mediates cholesterol metabolism by binding various receptors. The low-density lipoprotein receptor (LDLR) has a high affinity for apoE, and is the only member of its(More)
OBJECTIVE To examine the effects of apoB100 structure, specifically a mutation in the LDLr binding region, on the production of LDL and development of atherosclerosis in vivo. METHODS AND RESULTS Ldlr(-/-)Apobec1(-/-) mice lacking the LDLR and apoB editing enzyme accumulated LDL in plasma and developed severe atherosclerosis when they had wild-type(More)
Diabetes is a major risk factor for cardiovascular disease. To examine how diabetes interacts with a mildly compromised lipid metabolism, we introduced the diabetogenic Ins2(C96Y/+) (Akita) mutation into mice expressing human apoE4 (E4) combined with either an overexpressing human LDL receptor gene (hLDLR) or the wild-type mouse gene. The hLDLR allele(More)
Metabolic dysfunction, commonly a result of diets high in saturated fats and sugar, is associated with impaired cognitive function and an increased risk of age-related cognitive decline (ACD) and Alzheimer's disease (AD). Compared to the E3 isoform of apolipoprotein (apoE), the E4 isoform is a major genetic risk factor for ACD, AD, and for developing(More)