Abstract
Microbial attack on the brain has been suggested as a potential root-cause for dementia, including Alzheimer’s disease (AD), which is now the second leading cause of death in the UK. The defining diagnostic marker of AD is the presence of amyloid-β (Aβ) plaques in the brain. The precise physiological role of these plaques remains unclear, but recent work is suggesting a direct connection to bacterial infiltration of the brain. In this project you will explore the antimicrobial properties of Aβ peptides and determine their mechanisms of activity.
References
[1] Gilman S, Koller M, Black RS, Jenkins L, Griffith SG, Fox NC, Eisner L, Kirby L, Rovira MB, Forette F, Orgogozo JM, AN1792(QS-21)-201 Study Team (2005) Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial. Neurology 64, 1553-1562.
[2] Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, Michel BF, Boada M, Frank A, Hock C (2003) Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization. Neurology 61, 46-54
[3] Green RC, Schneider LS, Amato DA, Beelen AP, Wilcock G, Swabb EA, Zavitz KH, Tarenflurbil Phase 3 Study, Group (2009) Effect of tarenflurbil on cognitive decline and activities of daily living in patients with mild Alzheimer disease: A randomized controlled trial. JAMA 302, 2557-2564.
[4] Kagan BL, Jang H, Capone R, Arce FT, Ramachandran S, Lal R, Nussinov R (2012) Antimicrobial properties of amyloid peptides. Mol. Pharmaceutics 9, 708-717.
[5] Gostzyla ML, Brothers HM, Robinson SR. (2018) Alzheimer’s Amyloid-β is an antimicrobial peptide: A review of the evidence. J. Alzheimers Dis. 62, 1495-1506.