Genomic Analysis of Alzheimer’s Disease and Other Neurodegenerative Disorders

Event Details

Type

Friday Lecture Series

Speaker(s)

John Hardy, Ph.D., head, department of molecular neuroscience, chair, molecular biology of neurological disease, Institute of Neurology, University College London

Speaker bio(s)

Over the last eight years, whole genome analyses (genome wide association studies) and exome/genome sequencing studies have revolutionized our understanding of Alzheimer’s disease and the other common neurodegenerative diseases: Parkinson’s disease, motor neuron disease, and frontotemporal dementia. These recent investigations have complemented earlier studies where positional cloning allowed the identification of mendelian genes for these disorders. In this talk, Dr. Hardy will review the early data suggesting that increased production of Ab was the underlying mechanism for early onset disease and how this work underpinned the amyloid hypothesis for the disorder. While there have been findings suggesting this can contribute to late onset disease, the majority of findings have related to the innate immune system (largely microglia in the context of the brain) and lipid metabolism. Dr. Hardy will detail how these findings fit with the notion that amyloid deposition is at the heart of the pathogenesis of the disease. He will also discuss the possible reasons anti-amyloid therapies have so far failed, and what needs to be done to devise successful therapeutic approaches. Dr. Hardy will then briefly cover how in each of the other disorders, as loci for diseases are identified, their particular pathways can subsequently be mapped. These pathways reflect undying critical weaknesses in individual neuron types. For nigral neurons (PD) the critical failure point or “catastrophic cliff’ is mitophagy/autophagy; for pyramidal neurons (dementia), this is autophagy; for motor neurons and cortical neurons (ALS/FTD), this is the ubiquitin proteasome system; and for motor neurons this is the stress granule response. In each case, Dr. Hardy will outline how the genes his team has discovered fit into this scheme of selective vulnerability.

Dr. Hardy was the first to discover a mutation in the amyloid gene encoding the amyloid precursor protein (APP) which plays a key role in neurodegeneration associated with Alzheimer’s disease. His research interests are in the genetic analysis of disease. Historically, he has worked on the genetic analysis of Alzheimer's disease and other dementias and, more recently, on Parkinson's disease and other movement disorders and on motor neuron diseases.

Dr. Hardy has received a Piepenbrock-DZNE Award, a Breakthrough Prize in Life Sciences, a Helis Prize, and was jointly awarded the Brain Prize. He is a member of the Academy of Medical Sciences and Fellow of the Royal Society of London.

Open to

Public

Reception

Refreshments, 3:15 a.m. - 3:45 a.m., Abby Lounge

Contact

Justin Sloboda

Phone

(212) 327-7785

Sponsor

Justin Sloboda
(212) 327-7785
jsloboda@rockefeller.edu

Readings

http://librarynews.rockefeller.edu/?p=5545