UCLA Neuroscience Program Ph.D. Admissions Neuroscience Faculty UCLA and Beyond  

Karen Gylys
Synapse Pathology in Alzheimer's Disease

Email Address:  kgylys@sonnet.ucla.edu

Work Address:
Factor Building 6-266

Phone Numbers:
310 794-5472 laboratory
Phone Numbers:
310-206-3840 Office

Selected Publications:

Sokolow Sophie, Henkins Kristen M, Bilousova Tina, Miller Carol A, Vinters Harry V, Poon Wayne, Cole Gregory M, Gylys Karen Hoppens AD synapses contain abundant Aő≤ monomer and multiple soluble oligomers, including a 56-kDa assembly. Neurobiology of aging. 2012; 33(8): 1545-55.
Arold Stephen, Sullivan Patrick, Bilousova Tina, Teng Edmond, Miller Carol A, Poon Wayne W, Vinters Harry V, Cornwell Lindsey B, Saing Tommy, Cole Gregory M, Gylys Karen Hoppens Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex. Acta neuropathologica. 2012; 123(1): 39-52.
Ringman John M, Coppola Giovanni, Elashoff David, Rodriguez-Agudelo Yaneth, Medina Luis D, Gylys Karen, Cummings Jeffrey L, Cole Greg M Cerebrospinal fluid biomarkers and proximity to diagnosis in preclinical familial Alzheimer's disease. Dementia and geriatric cognitive disorders. 2012; 33(1): 1-5.
Ringman John M, Tomic Jennifer L, Coppola Giovanni, Elashoff David, Gylys Karen H, Glabe Charles G Conformation-dependent oligomers in cerebrospinal fluid of presymptomatic familial Alzheimer's disease mutation carriers. Dementia and geriatric cognitive disorders extra. 2012; 2(1): 652-7.
Henkins Kristen M, Sokolow Sophie, Miller Carol A, Vinters Harry V, Poon Wayne W, Cornwell Lindsey B, Saing Tommy, Gylys Karen Hoppens Extensive p-tau pathology and SDS-stable p-tau oligomers in Alzheimer's cortical synapses. Brain pathology (Zurich, Switzerland). 2012; 22(6): 826-33.
Sokolow Sophie, Henkins Kristen M, Williams Iris A, Vinters Harry V, Schmid Ingrid, Cole Gregory M, Gylys Karen H Isolation of synaptic terminals from Alzheimer's disease cortex. Cytometry. Part A : the journal of the International Society for Analytical Cytology. 2012; 81(3): 248-54.
Ringman John M, Frautschy Sally A, Teng Edmond, Begum Aynun N, Bardens Jenny, Beigi Maryam, Gylys Karen H, Badmaev Vladimir, Heath Dennis D, Apostolova Liana G, Porter Verna, Vanek Zeba, Marshall Gad A, Hellemann Gerhard, Sugar Catherine, Masterman Donna L, Montine Thomas J, Cummings Jeffrey L, Cole Greg M Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study. Alzheimer's research & therapy. 2012; 4(5): 43.
Ringman John M, Elashoff David, Geschwind Daniel H, Welsh Brian T, Gylys Karen H, Lee Cathy, Cummings Jeffrey L, Cole Greg M Plasma signaling proteins in persons at genetic risk for Alzheimer disease: influence of APOE genotype. Archives of neurology. 2012; 69(6): 757-64.
Sokolow Sophie, Luu Sanh H, Nandy Karabi, Miller Carol A, Vinters Harry V, Poon Wayne W, Gylys Karen H Preferential accumulation of amyloid-beta in presynaptic glutamatergic terminals (VGluT1 and VGluT2) in Alzheimer's disease cortex. Neurobiology of disease. 2012; 45(1): 381-7.
Ringman John M, Schulman Howard, Becker Chris, Jones Ted, Bai Yuchen, Immermann Fred, Cole Gregory, Sokolow Sophie, Gylys Karen, Geschwind Daniel H, Cummings Jeffrey L, Wan Hong I Proteomic changes in cerebrospinal fluid of presymptomatic and affected persons carrying familial Alzheimer disease mutations. Archives of neurology. 2012; 69(1): 96-104.
Ringman John M, Gylys Karen H, Medina Luis D, Fox Michelle, Kepe Vladimir, Flores Deborah L, Apostolova Liana G, Barrio Jorge R, Small Gary, Silverman Daniel H, Siu Erin, Cederbaum Stephen, Hecimovic Silva, Malnar Martina, Chakraverty Suma, Goate Alison M, Bird Thomas D, Leverenz James B Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimer's disease due to a novel PSEN1 mutation. Neuroscience letters. 2011; 487(3): 287-92.
Sokolow Sophie, Luu Sanh H, Headley Alison J, Hanson Alecia Y, Kim Taeree, Miller Carol A, Vinters Harry V, Gylys Karen H High levels of synaptosomal Na(+)-Ca(2+) exchangers (NCX1, NCX2, NCX3) co-localized with amyloid-beta in human cerebral cortex affected by Alzheimer's disease. Cell calcium. 2011; 49(4): 208-16.
Gylys, Karen H., Fein, Jeffrey A and Cole, Gregory M. Flow cytometric analysis of a crude synaptosomal fraction (P-2) from rat brain. Journal of Neurosci Res. Journal of Neurosci Res 2000; 61(8): 186-192.
Research Interest:

My laboratory studies pathways leading to synapse loss in Alzheimerís. Many in the field hold the hypothesis that Alzheimerís disease begins in the synapse, and itís important to define the earliest molecular changes, when there may be opportunity for reversal. My lab has developed methods for flow cytometry analysis of synaptosomes, which are resealed nerve terminals obtained by homogenization of brain in sucrose. We study postmortem human tissue from Alzheimerís and control patients, as well as transgenic mouse models of Alzheimerís disease. A main focus is the mechanism by which apolipoprotein E contributes to genetic risk for Alzheimerís.

My collaborative projects with the Mary S. Easton Center for Alzheimerís Research at UCLA are directed at finding CSF and blood biomarkers for early identification and monitoring of treatments in AD patients.

Recent findings of interest include the observation that amyloid beta is concentrated in a small population of apoE-positive synapses. Other recent studies in apoE-targeted replacement mice expressing human apoE show that the protective E2 allele enhances clearance of amyloid beta in the synaptic compartment. Our methods have potential application to a number of other conditions in which synaptic changes are thought to be important, including Parkinsonís disease, schizophrenia and drug abuse.

Techniques: synaptosome preparation; flow cytometry (also called fluorescence activated cell sorting (FACs) analysis) which enables precise quantification of markers of interest in large populations of (typically 5-10,000 particles/sample) of synaptosomes; immunolabeling techniques, confocal microscopy; also routine biochemical techniques including Western analysis, biochemical extractions, ELISA and multiplex (Luminex) assays for analytes of interest in blood and brain samples.