Patrick Sullivan

Journal article Behav Brain Res · November 21, 2008 Featured Publication Apolipoprotein (apo) E4, one of three human apoE (h-apoE) isoforms, has been identified as a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. However, the biological mechanisms involving apoE in learning a ... Full text Link to item Cite

Human apolipoprotein E4 targeted replacement mice show increased prevalence of intracerebral hemorrhage associated with vascular amyloid deposition.

Journal article J Stroke Cerebrovasc Dis · September 2008 Featured Publication Previous studies show that APOE *4 carriers are at increased risk for ischemic stroke and intracerebral hemorrhage (ICH). The APOE *4 gene is also linked to increased incidence of cerebral amyloid angiopathy. It has been suggested that apolipoprotein E4 ex ... Full text Link to item Cite

Mortalin is regulated by APOE in hippocampus of AD patients and by human APOE in TR mice.

Journal article Neurobiol Aging · December 2007 Featured Publication Mortalin is a chaperone protein associated with cell survival, stress response, intracellular trafficking, control of cell proliferation, mitochondrial biogenesis, and cell fate determination. Human APOE targeted replacement (TR) mice have been used to elu ... Full text Link to item Cite

Abeta42 neurotoxicity in primary co-cultures: effect of apoE isoform and Abeta conformation.

Journal article Neurobiol Aging · August 2007 Featured Publication Autosomal dominant mutations that increase amyloid-beta(1-42) (Abeta42) cause familial Alzheimer's disease (AD), and the most common genetic risk factor for AD is the presence of the epsilon4 allele of apolipoprotein E (apoE). Previously, we characterized ... Full text Link to item Cite

High-fat/high-cholesterol diet promotes a S1P receptor-mediated antiapoptotic activity for VLDL.

Journal article J Lipid Res · April 2007 Featured Publication Withdrawing growth factors or serum from endothelial cells leads to the activation of effector caspases 3 and 7, resulting in apoptotic cell death. HDL protects against caspase induction through sphingosine-1-phosphate (S1P) receptors. This anti-caspase ac ... Full text Link to item Cite

An apolipoprotein E-based therapeutic improves outcome and reduces Alzheimer's disease pathology following closed head injury: evidence of pharmacogenomic interaction.

Journal article Neuroscience · February 23, 2007 Featured Publication Apolipoprotein E (apoE) modifies glial activation and the CNS inflammatory response in an isoform-specific manner. Peptides derived from the receptor-binding region of apoE have been demonstrated to maintain the functional activity of the intact protein, a ... Full text Link to item Cite

Estradiol enhances long term potentiation in hippocampal slices from aged apoE4-TR mice.

Journal article Hippocampus · 2007 Featured Publication Hormone replacement therapy to treat or prevent Alzheimer Disease (AD) in postmenopausal women is controversial because it may pose other health risks such as cancer and thromboembolism. ApoE status is thought to influence the nootropic efficacy of hormone ... Full text Link to item Cite

Amyloid-beta1-42 reduces neuronal excitability in mouse dentate gyrus.

Journal article Neurosci Lett · July 31, 2006 Featured Publication Amyloid-beta (Abeta) is causally implicated in Alzheimer's disease and neuroplasticity failure has acquired validity as a possible mechanism of early AD pathogenesis. We have previously demonstrated that oligomeric Abeta(1-42) inhibits LTP in the dentate g ... Full text Link to item Cite

A deficit in astroglial organization causes the impaired reactive sprouting in human apolipoprotein E4 targeted replacement mice.

Journal article Neurobiol Dis · March 2006 Featured Publication The epsilon4 allele of apolipoprotein (apo)E associates with an increased risk of developing Alzheimer's disease (AD) as well as an earlier age of onset. However, the exact mechanisms by which apoE4 confers such susceptibility is currently unknown. We used ... Full text Link to item Cite

Apolipoprotein E allele-dependent pathogenesis: a model for age-related retinal degeneration.

Journal article Proc Natl Acad Sci U S A · August 16, 2005 Featured Publication Age-related macular degeneration (AMD) is a late-onset, multifactorial, neurodegenerative disease of the retina and the leading cause of irreversible vision loss in the elderly in the Western world. We describe here a murine model that combines three known ... Full text Link to item Cite

The low density lipoprotein receptor regulates the level of central nervous system human and murine apolipoprotein E but does not modify amyloid plaque pathology in PDAPP mice.

Journal article J Biol Chem · July 8, 2005 Featured Publication Apolipoprotein E (apoE), a chaperone for the amyloid beta (Abeta) peptide, regulates the deposition and structure of Abeta that deposits in the brain in Alzheimer disease (AD). The primary apoE receptor that regulates levels of apoE in the brain is unknown ... Full text Link to item Cite

Human apoE targeted replacement mouse lines: h-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior.

Journal article Behav Brain Res · April 15, 2005 Featured Publication Apolipoprotein E4 (apoE4), one of the three most common human apoE (h-apoE) isoforms, is a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. The biological mechanisms involving apoE in learning and memory p ... Full text Link to item Cite

Human apoE4-targeted replacement mice display synaptic deficits in the absence of neuropathology.

Journal article Neurobiol Dis · March 2005 Featured Publication The human APOE*4 allele is associated with an early age of onset and increased risk of Alzheimer's disease (AD). Long before the onset of AD, cognitive deficits can be identified in APOE*4 carriers. We examined neurons in the lateral amygdala of young apol ... Full text Link to item Cite

Production and characterization of astrocyte-derived human apolipoprotein E isoforms from immortalized astrocytes and their interactions with amyloid-beta.

Journal article Neurobiol Dis · 2005 Featured Publication The apolipoprotein E (apoE) genotype is an important genetic risk factor for Alzheimer's disease (AD). In the central nervous system (CNS), most apoE is produced by astrocytes and is present in unique high-density lipoprotein (HDL)-like particles that have ... Full text Link to item Cite

Marked regional differences of brain human apolipoprotein E expression in targeted replacement mice.

Journal article Neuroscience · 2004 Featured Publication We used three human apolipoprotein (apo) E targeted replacement mouse lines, each expressing one of the three common human apoE isoforms to study the pattern of apoE expression in the central nervous system (CNS). Immunocytochemistry on brain sections from ... Full text Link to item Cite

Purification and characterization of astrocyte-secreted apolipoprotein E and J-containing lipoproteins from wild-type and human apoE transgenic mice.

Journal article Neurochem Int · 2001 Featured Publication The varepsilon4 allele of apolipoprotein E (apoE) is a genetic risk factor for Alzheimer's disease (AD). In order to gain a better understanding of the molecular mechanisms by which apoE and possibly other apolipoproteins produced in the central nervous sy ... Full text Link to item Cite

Apo E structure determines VLDL clearance and atherosclerosis risk in mice.

Journal article J Clin Invest · June 1999 Featured Publication We have generated mice expressing the human apo E4 isoform in place of the endogenous murine apo E protein and have compared them with mice expressing the human apo E3 isoform. Plasma lipid and apolipoprotein levels in the mice expressing only the apo E4 i ... Full text Link to item Cite

Type III hyperlipoproteinemia and spontaneous atherosclerosis in mice resulting from gene replacement of mouse Apoe with human Apoe*2.

Journal article J Clin Invest · July 1, 1998 Featured Publication To study isoform-specific effects of apolipoprotein E (apoE) in vivo, we generated mice with a human APOE*2 allele in place of the mouse Apoe gene via targeted gene replacement in embryonic stem cells. Mice expressing human apoE2 (2/2) have virtually all t ... Full text Link to item Cite

Targeted replacement of the mouse apolipoprotein E gene with the common human APOE3 allele enhances diet-induced hypercholesterolemia and atherosclerosis.

Journal article J Biol Chem · July 18, 1997 Featured Publication Apolipoprotein (apo) E, a constituent of several lipoproteins, is a ligand for the low density lipoprotein receptor, and this interaction is important for maintaining cholesterol and triglyceride homeostasis. We have used a gene replacement strategy to gen ... Full text Link to item Cite