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Alzheimer's disease (AD) is the most common among these, and consequently significant research effort is spent on studying it. Although a lot is known about the pathology of AD and the role of \u03b2-amyloid (A\u03b2) peptides, the complete network of interactions regulating A\u03b2 metabolism and toxicity still eludes us. To address this, we have conducted genetic interaction screens using transgenic Drosophila expressing A\u03b2 and we have identified mutations that affect A\u03b2 metabolism and toxicity. These analyses highlight the involvement of various biochemical processes such as secretion, cholesterol homeostasis, and regulation of chromatin structure and function, among others, in mediating toxic A\u03b2 effects. Several of the mutations that we identified have not been linked to A\u03b2 toxicity before and thus constitute novel potential targets for AD intervention. We additionally tested these mutations for interactions with tau and expanded-polyglutamine overexpression and found a few candidate mutations that may mediate common mechanisms of neurodegeneration. Our data offer insight into the toxicity of A\u03b2 and open new areas for further study into AD pathogenesis<\/jats:p>","DOI":"10.1534\/genetics.107.078394","type":"journal-article","created":{"date-parts":[[2008,2,4]],"date-time":"2008-02-04T01:28:41Z","timestamp":1202088521000},"page":"1457-1471","source":"Crossref","is-referenced-by-count":85,"title":["Identification of Novel Genes That Modify Phenotypes Induced by Alzheimer's \u03b2-Amyloid Overexpression in Drosophila"],"prefix":"10.1093","volume":"178","author":[{"given":"Weihuan","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Genetics , Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho-Juhn","family":"Song","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research , Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Gangi","sequence":"additional","affiliation":[{"name":"Department of Genetics , Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anju","family":"Kelkar","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research , Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isha","family":"Antani","sequence":"additional","affiliation":[{"name":"Department of Genetics , Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Garza","sequence":"additional","affiliation":[{"name":"Novartis Institutes for Biomedical Research , Cambridge, Massachusetts 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Konsolaki","sequence":"additional","affiliation":[{"name":"Department of Genetics , Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854 and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,3,1]]},"reference":[{"key":"2023030409453221100_","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3233\/JAD-2006-102-303","volume":"10","year":"2006","journal-title":"J. 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