What causes Alzheimer's and how
do we find a cure? This project aims to pinpoint underlying molecular
causes of Alzheimer's Disease by direct coupling of clinical data for patients
suffering from genetic forms of the disease with the chemical properties of the
protein mutants that these patients carry.
This coupling is a unique
technique developed by our research group at DTU which has led to a range of
recent breakthroughs in the understanding of the disease in 2015 and 2016 (1,2,3,4).
Disease is a devastating neurodegenerative disease and one of the major
challenges of this century, with millions of people affected world-wide and
prevalence growing steadily (5,6,7).
The specific objectives of this
project are 1) to construct a major database of Alzheimer’s Disease including both
clinical data (survival times, age of
diagnosis/onset) for patients who have inherited Alzheimer's and the associated
chemical properties of the
corresponding protein variants; 2) show that statistically significant correlations
exist between these two types of data; 3) identify the protein properties that
correlate with disease. These properties can then be used to develop biomarkers
for early-stage diagnosis and in future drug discovery programs directed
towards treating this terrible neuro-degenerative disease.
The project involves a range of
bioinformatics tools, physical chemistry and computational chemistry techniques
and can vary in difficulty from undergraduate and bachelor students, to master
(1) Somavarapu, A. K.; Kepp, K. P. The
Dynamic Mechanism of Presenilin-1 Function: Sensitive Gate Dynamics and
Loop Unplugging Control Protein Access. Neurobiol.
Dis. 2016, 89, 147–156.
(2) Somavarapu, A. K.; Kepp, K. P. Loss of
Stability and Hydrophobicity of Presenilin 1 Mutations Causing Alzheimer’s
Disease. J. Neurochem. 2016.
(3) Tiwari, M. K.; Kepp, K. P. β-Amyloid
Pathogenesis: Chemical Properties versus Cellular Levels. Alzheimer’s Dement.
J. Alzheimer's Assoc. 2016, 12 (2), 184–194.
(4) Somavarapu, A. K.; Kepp, K. P. Direct
Correlation of Cell Toxicity to Conformational Ensembles of Genetic Abeta
Variants. ACS Chem. Neurosci. 2015, 6, 1990–1996.
(5) Goedert, M.; Spillantini, M. G. A
Century of Alzheimer’s Disease. Science 2006, 314 (2006),
(6) Kepp, K. P. Bioinorganic Chemistry of
Alzheimer’s Disease. Chem. Rev. 2012, 112 (10), 5193–5239.
(7) Kepp, K. P. Alzheimer’s Disease due to
Loss of Function: A New Synthesis of the Available Data. Prog. Neurobiol.
2016, 143, 36–60.
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