Neuropathology, AD Prevention, Clinical trials, Epidemiology, Chemistry/Pharmacology, A-beta PP/A-beta
Researcher Bio BS ChE, MSChE
Design and build chemical and energy plants in U.S. and 24 other countries. Turning career long problem solving to Alzheimer's prevention.
Translation of fundamental chemistry developments in organic inorganic, biochemical science to commercial production scale.
What is the greatest void to date in our knowledge of Alzheimer's Disease? Cause(s)
What are the top three papers (not yours) you have read recently? NEJM Nov. 21, 2001 Erasmus Medical Center's Rotterdam Study respecting NSAID dementia risk reduction.
S.Weggen, Golde, Koo et. al. Nature 8, November 2001 NSAID subset lowers Ab42 independent of inflamation activity.
Schenk, D. Amyloid-beta Immunotherapy for AD: End of the Beginning. Neuroscience October 2002
If resources were not limited, what research projects would you pursue? Prevention mechanism of select NSAIDs from Weggan et al and EMC's data sets.
Immunotherapy trial options to control brain inflamatory response.
What is your leading hypothesis? Everybodys Blood Brain Barrier (BBB) tightens with age, interfering with general brain perfusion but more importantly with inhibiting clearance through diffusion of Beta Amyloid oligimers. APOE genotypes have different BBB tightening timetables with homo E4 the earliest (67-72), hetro E4 later (73-78), E3's later still (79-84) and E2's (85+).
Clearance restrictions leads to extensive Beta amyloid polymer deposition, with inflammatory response to macrophage depolymerization. Process accelerates with no outlet for polymer/oligimers, into the cascade which involves neuron unraveling into tau, and snaptic junction corruption.
What piece of missing evidence would help prove it? Familial AD prevention or significant (decade)delay with ab 42 functional NSAID.
What is your fallback position? Premature death with AD or its complications.