Specific Alterations of Tau Phosphorylation and Neuronal Signaling Induced by the Amyloid-β Oligomer Aβ*56
Undergraduate Institution and Major/Degree:
- CUNY Hunter College, BA, Psychology, 2010
Postdoctoral Associate, Columbia University
For nearly a century, amyloid plaques have been thought to be the bioactive agents in Alzheimer's disease (AD). However, numerous studies in the past decade have supported the notion that the soluble forms of the amyloid-Î² (AÎ²) peptides, called AÎ² oligomers, were responsible for AD-associated memory impairment. I am interested in the molecular mechanism by which AÎ² leads to the neuropathology that leads to the cognitive decline in AD. In particular, the oligomer AÎ²*56 (a 56KDa oligomer of AÎ²) was found to cause cognitive decline in the AD mouse model Tg2576 in absence of plaques and neuronal loss. How AÎ²*56 is able to disrupt cognition at the cellular level remains unknown to this date. My current focus is to identify the molecular mechanism by which AÎ²*56 is causing cognitive impairment in what seems to be preclinical AD.
- Michael Lee
- Sylvain Lesne
- Lorene Lanier
- Yashushi Nakagawa
Courses Taken Beyond the Core Courses:
- Neurobiology of Diseases
- Signal Transduction/Gene Expression
- Michael Lee-Chair
- Sylvain Lesne-Advisor
- Karen Ashe
- Harry Orr
- Eric Newman
- Dominic Walsh-External Member
- Society for Neuroscience meeting 2011 & 2014
- Larson ME, Greimeal SJ, Amar F, LaCroix M, Boyle G et al. Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits. Proc Natl Acad Sci USA. 2017;114:E4648-4657.
- Amar F, Sherman MA, Rush T, Larson M, Boyle G, Change L, Gotz J, Buisson A, Lesne SE. The amyloid-β oligomer Aβ*56 induces specific alterations in neuronal signaling that lead to tau phosphorylation and aggregation. Sci Signal. 2017;10(478). pii. eaaa12021.
- Sherman MA, LaCruoix M, Amar F, Larson ME, Forster C, Aguzzi A, Bennett DA, Ramsden M, Lesne SE. Soluble confromers of aB and tau alter selective proteins governing axonal transport. J Neurosci. 2016;36:9647-9658.
- Larson M, Sherman MA, Amar F, Nuvolone M, Schneider JA, Bennett DA, Aguzzi A, Lesne SE. The complex PrP(c)-Fyn couples human oligomeric AB with pathological tau changes in Alzheimer's disease. J. Neurosci. 2012;32:16857-16871.
Awards and Honors:
- Roth-Steer Award for Research in Alzheimer's Disease, 2015
- American Legion Family Brain Sciences Student Award, 2014
- Community of Scholars Program Travel Award, 2014
- NIH T32 Training Grant 2012/2013
- Dakar, Senegal