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F4‐04‐04: Subcortical Shape Analysis for Joint Biomarker Discovery
Author(s) -
Gutman Boris A.,
Ragothaman Anjani,
Riedel Brandalyn,
Ching Christopher,
Thompson Paul M.
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.603
Subject(s) - false discovery rate , putamen , biomarker , region of interest , neuroimaging , multiple comparisons problem , medicine , imaging biomarker , neuroscience , amygdala , biomarker discovery , nuclear medicine , magnetic resonance imaging , psychology , biology , radiology , gene , mathematics , genetics , statistics , proteomics
not available. PL-04-02 GENOMIC ANALYSIS OF NEURODEGENERATION GIVES CLUES TO PATHWAYS TO SELECTIVE CELL LOSS: THE HYPOTHESIS OF THE CATASTROPHIC CLIFF OF NEURON FAILURE John Hardy, UCL Institute of Neurology, London, United Kingdom. Contact e-mail: j.hardy@ucl.ac.uk Background:As we identify large numbers of genes involved in different syndromes, we are realising that these genes mark specific biochemical pathways. In Alzheimer’s disease, these are APP processing, cholesterol metabolism, microglial/monocyte activation and the ubiquitin proteasome system. In Parkinson’s disease, they are autophagy and mitophagy. Methods: The simplest interpretation of these data is that genetic variability in these pathways influences disease risk and that pharmacologic manipulation of these pathways constitute valid targets for their treatment. A deeper truth, however, also appears to come from this richness of genetic data: as we identify multiple genes for syndromes, we see that different neutron types fail in the context different lesions. Results: These catastrophic failure points include calcium homeostasis and DNA repair for Purkinje cells, the ubiquitin proteasome system for granule cells, mitochondrial complex 1 for nigral neurons, the lysosome for cortical pyramidal neurons, and the ubiquitin proteasome system for the cortical pyramidal neurons and motor neurons and RNA processing for motor neurons. Conclusions: Thus, each of these cell types is prone to be closer to failure under different stressors. Understanding these selective weaknesses offers a route to the development of rational neuroprotective strategies. WEDNESDAY, JULY 27, 2016