D
David R. Howlett
Researcher at Wolfson Centre for Age-Related Diseases
Publications - 56
Citations - 4486
David R. Howlett is an academic researcher from Wolfson Centre for Age-Related Diseases. The author has contributed to research in topics: Lewy body & Dementia. The author has an hindex of 27, co-authored 55 publications receiving 4146 citations. Previous affiliations of David R. Howlett include GlaxoSmithKline & King's College London.
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Journal ArticleDOI
Identification of a novel aspartic protease (Asp 2) as beta-secretase.
Ishrut Hussain,David J. Powell,David R. Howlett,David G. Tew,Thomas D. Meek,Conrad Gerald Chapman,Israel S. Gloger,Kay Elizabeth Murphy,Christopher Southan,Dominic M. Ryan,Trudi S. Smith,David Simmons,Frank S. Walsh,Colin Dingwall,Gary Christie +14 more
TL;DR: Asp 2, a novel transmembrane aspartic protease, has the key activities expected of β-secretase, and mutation of either of the putative catalytic aspartyl residues in Asp 2 abrogates the production of the fragments characteristic of cleavage at the β- secretase site.
Journal ArticleDOI
Association of plasma clusterin concentration with severity, pathology, and progression in Alzheimer disease
Madhav Thambisetty,Andrew Simmons,Latha Velayudhan,Abdul Hye,James Campbell,Yi Zhang,Lars-Olof Wahlund,Eric Westman,Anna Kinsey,Andreas Güntert,Petroula Proitsi,John Powell,Mirsada Causevic,Richard Killick,Katie Lunnon,Steven Lynham,Martin Broadstock,Fahd Choudhry,David R. Howlett,Robert J. Williams,Sally I. Sharp,Cathy Mitchelmore,Catherine Tunnard,Rufina Leung,Catherine Foy,Darragh O'Brien,Gerome Breen,Simon J. Furney,Malcolm Ward,Iwona Kłoszewska,Patrizia Mecocci,Hilkka Soininen,Magda Tsolaki,Bruno Vellas,Angela Hodges,Declan G. Murphy,Sue Parkins,Jill C. Richardson,Susan M. Resnick,Luigi Ferrucci,Dean F. Wong,Yun Zhou,Sebastian Muehlboeck,Alan C. Evans,Paul T. Francis,Christian Spenger,Simon Lovestone +46 more
TL;DR: These results demonstrate an important role of clusterin in the pathogenesis of AD and suggest that alterations in amyloid chaperone proteins may be a biologically relevant peripheral signature of AD.
Journal ArticleDOI
Cognitive correlates of Aβ deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes
David R. Howlett,Jill C. Richardson,Angela A Austin,Andrew A. Parsons,Simon T. Bate,D. Ceri Davies,M. Isabel Gonzalez +6 more
TL;DR: The results suggest that the cognitive impairment in TASTPM mice is related to the disruption of neural connectivity and not simply Abeta deposition, which first occurs 3 months earlier.
Journal ArticleDOI
Inhibition of fibril formation in beta -amyloid peptide by a novel series of benzofurans
David R. Howlett,Amanda E. Perry,Fiona Godfrey,Jane E. Swatton,Kevin H. Jennings,Claus Spitzfaden,Harry John Wadsworth,Stephen J. Wood,Roger Edward Markwell +8 more
TL;DR: There is a close correlation between the activity of the benzofurans as inhibitors of fibril formation and their ability to bind to beta-amyloid, as identified by scintillation proximity binding assay and NMR studies.
Journal ArticleDOI
ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site.
Ishrut Hussain,David J. Powell,David R. Howlett,G A Chapman,L Gilmour,P R Murdock,David G. Tew,Thomas D. Meek,Conrad Gerald Chapman,Klaus Schneider,S J Ratcliffe,D Tattersall,T T Testa,Christopher Southan,Desmond Ryan,David Simmons,Frank S. Walsh,Colin Dingwall,Gary Christie +18 more
TL;DR: The characterization of a second highly related aspartic proteinase, Asp1, is described as a second β-secretase candidate and has the N-terminal sequence ALEP… , indicating that it has lost the prodomain.