Thesis (Ph. D.)--Case Western Reserve University, 2007. / [School of Medicine] Department of Neurosciences. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Stockholms universitet, 2006. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of South Florida, 2004. / Includes vita. Includes bibliographical references (leaves 183-193). Also available online.

Hao, Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 98-115). / Abstracts in English and Chinese. / Acknowledgement --- p.i / Abstract --- p.iii / 摘要 --- p.v / List of Abbreviations --- p.vii / List of Figures --- p.x / List of Tables --- p.xi / List of Primers --- p.xii / Publications arising from this study --- p.xiii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Alzheimer's disease --- p.1 / Chapter 1.2 --- APP and its functions --- p.4 / Chapter 1.2.1 --- APP processing --- p.7 / Chapter 1.3 --- APPc-interacting proteins --- p.10 / Chapter 1.3.1 --- FE65 --- p.10 / Chapter 1.3.2 --- Xllα and Xl1β --- p.12 / Chapter 1.3.3 --- JIP-1 --- p.13 / Chapter 1.3.4 --- Dabl and Dab2 --- p.15 / Chapter 1.3.5 --- SNX17 --- p.15 / Chapter 1.3.6 --- Numb --- p.15 / Chapter 1.3.7 --- AIDA-1 --- p.16 / Chapter 1.4 --- Objectives of the project --- p.18 / Chapter 1.4.1 --- Engulfment adaptor protein 1 (GULP1) --- p.19 / Chapter 1.4.2 --- Specific aims of my study --- p.20 / Chapter Chapter 2 --- General Methodology --- p.22 / Chapter 2.1 --- Bacterial culture --- p.22 / Chapter 2.2 --- Mini-preparation/Midi-preparation of plasmid DNA --- p.22 / Chapter 2.3 --- Spectrophotometric analysis of DNA --- p.22 / Chapter 2.4 --- Agarose gel electrophoresis for DNA --- p.23 / Chapter 2.5 --- Preparation of competent E. coli --- p.23 / Chapter 2.6 --- Transformation of competent E. coli --- p.24 / Chapter 2.7 --- Molecular cloning --- p.24 / Chapter 2.7.1 --- Preparation of the cloning vector and insert --- p.25 / Chapter 2.7.2 --- Isolation of DNA from agarose gel --- p.25 / Chapter 2.7.3 --- DNA ligation and transformation --- p.25 / Chapter 2.7.4 --- Rapid screening for ligated plasmid --- p.26 / Chapter 2.8 --- Site-directed mutagenesis --- p.26 / Chapter 2.9 --- Cell culture and transfection --- p.27 / Chapter 2.10 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS/PAGE) --- p.28 / Chapter 2.11 --- Western blotting --- p.29 / Chapter Chapter 3 --- Investigation of the GULP1-APP interaction and the effect of GULP1 on APP processing --- p.31 / Chapter 3.1 --- Introduction --- p.31 / Chapter 3.2 --- Materials and methods --- p.34 / Chapter 3.2.1 --- DNA constructs --- p.34 / Chapter 3.2.2 --- Antibodies --- p.34 / Chapter 3.2.3 --- GST pull-down assays --- p.35 / Chapter 3.2.4 --- Rat tissues preparation --- p.36 / Chapter 3.2.5 --- Immunostaining --- p.36 / Chapter 3.2.6 --- "siRNA knockdown of GULPl in CHO, HEK293 and SHSY5Y cells" --- p.37 / Chapter 3.2.7 --- Luciferase assays --- p.37 / Chapter 3.2.9 --- Tricine-SDS/PAGE analysis for APP CTFs --- p.38 / Chapter 3.2.9 --- Aβ enzyme-linked immunosorbent assay (ELISA) --- p.39 / Chapter 3.2.10 --- Statistical analysis --- p.40 / Chapter 3.3 --- Results --- p.40 / Chapter 3.3.1 --- GULP1 F145V mutant abandons the GULP1-APP interaction --- p.40 / Chapter 3.3.2 --- GULP1 and APP colocalize in neurons --- p.45 / Chapter 3.3.3 --- "siRNA mediated knockdown of GULPl in CHO, HEK293 and SHSY5Y cells" --- p.48 / Chapter 3.3.4 --- GULP1 enhances the cleavage of APP in APP-GAL4 cleavage system --- p.49 / Chapter 3.3.5 --- GULP1 alters APP processing by increasing the secretion of APP CTFs --- p.52 / Chapter 3.3.6 --- GULP1 stimulates Aβ secretion --- p.55 / Chapter 3.4 --- Discussion --- p.57 / Chapter Chapter 4 --- Identification and characterization of GULPl phosphorylation sites --- p.60 / Chapter 4.1 --- Introduction --- p.60 / Chapter 4.2 --- Materials and Methods --- p.60 / Chapter 4.2.1 --- DNA constructs --- p.61 / Chapter 4.2.2 --- Antibodies --- p.61 / Chapter 4.2.3 --- Expression and purification of GST fusion proteins --- p.61 / Chapter 4.2.4 --- In vitro phosphorylation of GULP1 by cdk5/p35 --- p.62 / Chapter 4.3 --- Results --- p.62 / Chapter 4.3.1 --- GULP1 Ser223 can be phosphorylated by cdk5/p35 in vivo --- p.62 / Chapter 4.3.2 --- The phosphorylation ofGULPl Thr35 completely abolished the GULP1-APP interaction --- p.67 / Chapter 4.4 --- Discussion --- p.70 / Chapter Chapter 5 --- Crystallization of the PTB domains of GULPl and GULP1t35d…… --- p.72 / Chapter 5.1 --- Introduction --- p.72 / Chapter 5.2 --- Materials and Methods --- p.72 / Chapter 5.2.1 --- DNA constructs --- p.72 / Chapter 5.2.2 --- Small-scale protein expression and purification --- p.73 / Chapter 5.2.3 --- Large-scale protein expression and purification --- p.73 / Chapter 5.2.4 --- Dynamic light scattering measurement --- p.76 / Chapter 5.2.5 --- Crystallization screening GULP1-PTB --- p.76 / Chapter 5.2.6 --- Optimization of GULP1-PTB crystals by grid screen --- p.76 / Chapter 5.2.7 --- Optimization of GULPl -PTB crystals by additive screen and detergent screen --- p.79 / Chapter 5.3 --- Results --- p.79 / Chapter 5.3.1 --- Large-scale expression and purification of GULP 1-PTB --- p.79 / Chapter 5.3.2 --- Small-scale expression and purification of GULP1T35d-PTB --- p.86 / Chapter 5.3.3 --- Crystallization screening and optimization --- p.88 / Chapter 5.4 --- Discussion --- p.91 / Chapter Chapter 6 --- Conclusion and future perspective --- p.94 / Chapter 6.1 --- Conclusion --- p.94 / Chapter 6.2 --- Future perspective --- p.95 / References --- p.98

Dissertation (Ph.D.)--University of South Florida, 2008. / Includes vita. Includes bibliographical references.

Thesis (Ph.D.)--University of South Florida, 2004. / Includes vita. Includes bibliographical references (leaves 144-164).

Cheng, Wai Hang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 76-88). / Abstract also in Chinese. / Acknowledgement --- p.i / 摘要 --- p.iii / List of Abbreviations --- p.iv / List of Figures --- p.vi / List of Tables --- p.vii / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- FE65 --- p.1 / Chapter 1.1.1 --- FE65 Protein Family and Their Structures --- p.2 / Chapter 1.1.1.2 --- PTB domains --- p.5 / Chapter 1.1.2 --- Expression Pattern of FE65 Proteins --- p.6 / Chapter 1.1.3 --- FE65 Family-Transgenic Animals --- p.7 / Chapter 1.1.4 --- Interacting Partners of FE65 --- p.8 / Chapter 1.1.4.1 --- "APP, APLPl and APLP2" --- p.9 / Chapter 1.1.4.2 --- LRP1 and ApoEr2 --- p.10 / Chapter 1.1.4.3 --- c-Abl --- p.11 / Chapter 1.1.4.4 --- Mena and EVL --- p.11 / Chapter 1.1.4.5 --- Tip60 --- p.12 / Chapter 1.1.4.6 --- SET --- p.12 / Chapter 1.1.4.7 --- Estrogen Receptor a --- p.13 / Chapter 1.1.4.8 --- Teashirt --- p.13 / Chapter 1.1.4.9 --- CP2/LSF/LBP1 --- p.13 / Chapter 1.1.4.10 --- Dexra sl --- p.14 / Chapter 1.1.4.11 --- P2X2-receptor subunit --- p.14 / Chapter 1.1.4.12 --- Tau --- p.15 / Chapter 1.1.4.13 --- Notchl --- p.15 / Chapter 1.1.4.14 --- Alcadein --- p.16 / Chapter 1.1.4.15 --- CD95/Fas/Apo -1 ligand --- p.16 / Chapter 1.1.4.16 --- p68 subunit of pre -mRNA cleavage and polyadenylation factor Im (p68 CFIm) --- p.17 / Chapter 1.1.4.17 --- Ataxinl --- p.17 / Chapter 1.1.5.1 --- FE65 as an adaptor protein --- p.20 / Chapter 1.1.5.2 --- FE65 and Alzheimer´ةs disease --- p.20 / Chapter 1.1.5.3 --- Transcriptional / Post-transcriptional regulation --- p.22 / Chapter 1.1.5.4 --- Apoptosis and cell cycle regulation --- p.23 / Chapter 1.1.5.5 --- Neuronal positioning and cell migration --- p.23 / Chapter 1.1.5.6 --- Learning and memory --- p.25 / Chapter 1.2 --- Objectives --- p.26 / Chapter Chapter 2 --- Investigation of the interaction between FE65 and Arf6 --- p.27 / Chapter 2.1 --- Materials --- p.27 / Chapter 2.1.1 --- DNA contructs --- p.27 / Chapter 2.1.2 --- Cell culture --- p.27 / Chapter 2.1.3 --- Immunoblotting --- p.28 / Chapter 2.1.4 --- Miscellaneous --- p.28 / Chapter 2.2 --- Methods --- p.29 / Chapter 2.2.1 --- Preparation of Escherichia coli competent cells --- p.29 / Chapter 2.2.2 --- DNA preparation with Intron Plasmid DNA --- p.30 / Chapter 2.2.3 --- DNA preparation with Macherey-Nagel NucleoBond Xtra Midi --- p.30 / Chapter 2.2.4 --- DNA preparation by the alkaline lysis method --- p.31 / Chapter 2.2.5 --- Spectrophotometric analysis of DNA --- p.32 / Chapter 2.2.6 --- Agarose gel electrophoresis --- p.32 / Chapter 2.2.7 --- Cell culture and transfection --- p.33 / Chapter 2.2.8 --- Bacterial GST-pull down assay --- p.33 / Chapter 2.2.9 --- GST-pull down assay for testing direct interaction between FE65 and Arf6 --- p.34 / Chapter 2.2.10 --- Mammalian GST-pull down assay --- p.35 / Chapter 2.2.11 --- Immunoprecipitation --- p.36 / Chapter 2.2.12 --- SDS-PAGE --- p.36 / Chapter 2.2.13 --- Immunoblotting --- p.39 / Chapter 2.3 --- Results --- p.40 / Chapter 2.3.1 --- Interaction between Arf6 and FE65 --- p.40 / Chapter 2.3.2 --- Determination of the interacting domain of FE65 with Arf6 --- p.43 / Chapter 2.3.3 --- Determination if FE65 and Arf6 interact directly --- p.45 / Chapter Chapter 3 --- Production of Antisera against Arf6 and Immunostaining of FE65-Arf6 --- p.47 / Chapter 3.1 --- Materials --- p.47 / Chapter 3.1.1 --- Protein expression and purification --- p.47 / Chapter 3.1.2 --- Immunization and harvest of antisera --- p.48 / Chapter 3.1.3 --- Immunostaining --- p.48 / Chapter 3.2 --- Methods --- p.48 / Chapter 3.2.1 --- Protein expression and purification --- p.48 / Chapter 3.2.2 --- Bradford assay --- p.50 / Chapter 3.2.3 --- Immunization --- p.50 / Chapter 3.2.4 --- Antibody purification --- p.51 / Chapter 3.2.5 --- Immunostaining --- p.52 / Chapter 3.3 --- Results --- p.53 / Chapter 3.3.1 --- Recombinant Arf6 expression and purification --- p.53 / Chapter 3.3.2 --- Titering of antisera --- p.57 / Chapter 3.3.3 --- Determination of antisera specificity --- p.59 / Chapter Chapter 4 --- Discussion --- p.68 / Chapter Chapter 5 --- Future Perspectives --- p.73 / References --- p.76

Thesis (Ph. D.)--University of Oklahoma. / Bibliography: leaves 122-136.

Mutations of three genes encoding amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2) have been shown to reliably result in familial early-onset Alzheimer's disease (FAD); a rare, but catastrophic, subtype of Alzheimer's disease (AD) marked by symptom emergence before age 65 as well as accelerated cognitive deterioration. The current study represents the first known meta-analysis on the association of APP, PSEN1 or PSEN2 on neurocognitive variables. A total of 278 FAD mutation-carriers (FAD-MC) and 284 cognitively healthy non-mutation-carriers (NC) across 10 independent investigations meeting inclusion criteria were chosen for the current meta-analysis (random effects design). Findings revealed an overarching trend of poorer performance by FAD-MC individuals compared to NC individuals across the majority of cognitive domains identified. Significant differences in effect sizes suggested FAD-MC individuals exhibited worse performance on measures of attention, explicit memory, fluency, primary memory, verbal, and visuospatial functioning. Findings indicative of differential sensitivity to cognitive domain impairments across FAD-MC and NC groups inform neuropsychological descriptions of individuals in preclinical phases of FAD.