Updated 27 October 2011
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We list here a collection of special seminars, on-line journal club discussions,
recorded talks and other presentations on the Forum web site that describe a
variety of scientific hypotheses about the pathogenesis of Alzheimer's disease.
Over time, we intend to represent a more comprehensive range of theories. We
hope that readers will be stimulated to think more broadly about this many-faceted
disorder and to consider how this diversity of ideas and data may be integrated
into a more complete picture of the disease.
We have also created the Hypothesis Factory that
is devoted to the presentation and exchange of ideas regarding novel hypotheses,
hunches, theories-in-progress, etc. The Hypothesis Factory is a forum where
people with original or unconventional ideas can publicly present and discuss
Submit a hypothesis. We invite your comments and questions.
The Aging Factor Cascade Hypothesis (AFCH)
By Jonathan Brouillette—Updated 30 October 2013
AD, PD, HD, ALS, FTLD-U, CJD and RSA Are Autoimmune Disorders: A Unifying Hypothesis on the Function of Aß, Tau, a-Synuclein, Huntingtin, TDP-43, PrP, and AA in Innate Immunity
By Claudiu Bandea, Centers for Disease Control and Prevention, Atlanta, Georgia—Updated 27 October 2011
Aβ-mediated Crosslinking May Regulate TrkA-p75 Association and Cooperations of p75 With APP, Prion, and Synuclein
By Rudolf Bloechl, independent investigator, Germany—Updated 1 February 2010
Chronic Stress Hypothesis of AD
By Tohru Hasegawa, Saga Woman Junior College, Saga, Japan—Posted 7 April 2007
At a Crossroad of Amyloid-β Functional Pathways: Homeostasis of cholesterol and lipid peroxidation are integrated components of neural membrane neuroplasticity mechanisms and neurodegeneration
—Updated 26 November 2005
By Alexei Koudinov and Natalia Koudinova
Apolipoprotein E, Alzheimer Disease, and Cerebral Amyloid Angiopathy: Effects of ApoE on Amyloid-β Metabolism Suggest Underlying Mechanisms and Potential Treatments (.pdf)
—Posted 15 August 2005
By David M. Holtzman
Axonal Transport Dysfunction Hypothesis—Posted 7 July 2005
By John Trojanowski
"The Amyloid Cascade Hypothesis"—Updated 23 May 2005
By Dennis Selkoe.
Arguments Against the Amyloid Cascade Hypothesis
Ipsen Foundation Symposium:
"Connections, Cognition And Alzheimer's Disease"
A major theme in many of the speakers is that cognitive impairment in Alzheimer's disease is referable to loss of specific populations of projection neurons and the breakdown of highly vulnerable neural systems, especially those involved in memory formation. There is general consensus among these speakers that these neuronal alterations occur largely independent of amyloid deposition.
"Alzheimer's disease: a re-examination of the amyloid hypothesis"
By R.L. Neve and N.K. Robakis. Live journal club discussion March 1998.
"Does beta amyloid kill from within the cell or from the extracellular space?"
A live debate by Steven Younkin and Dennis Selkoe. September 1997.
Debate: The Amyloid Cascade Hypotheses 10 Years Later
Chaired by Price, D. (Baltimore, MD, US) Wurtman, R.J. (Boston, MA,US).
Two Hits and You're Out? A Novel Mechanistic Hypothesis of Alzheimer Disease—Posted 23 October 2004
By Xiongwei Zhu, George Perry, Mark A. Smith, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
The Pathogen Hypothesis—1 July 2004
By Brian Balin, Denah Appelt, Joseph Lyons, Ruth Itzhaki, and Curtis Dobson
Aluminosilicate Precipitation and Alzheimer's Disease—Updated 14 July 2005
By Colin Meyer
Is Alzheimer's an Autoimmune Disease?—Posted 12 February 2004
By Michael R. D'Andrea, Ph.D., Principal Scientist, J&J Pharmaceutical Research and Development
Disruption of Glial (oligodendrocyte and astrocyte) Cellular Function ...—Posted 19 August 2003
By Steven Brenner, Affiliated with Neurology Departments at the Saint Louis VA Medical
Center and Saint Louis University Medical Center
The Combination of Nicotine with Galantamine Is Expected to Have Enhanced Therapeutic Effects in Patients with Alzheimer's Disease—Posted 5 December 2003
By Silvia Petrova
Viruses and Dementia, and the Role of Apolipoprotein E (ApoE)—Posted 15 June 2002
By Ruth Itzhaki, University of Manchester Institute of Science and Technology
Polymorphisms in Inflammatory Genes Enhance the Risk of Alzheimer Disease—Posted 11 February 2002
By P.L. McGeer and E.G. McGeer, Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, B.C., Canada
Advanced Aging Plus "Risk Factors" May Explain Late-Onset Spordic Alzheimer's Disease—Updated 8 May 2002
By Ming Chen, VA Medical Center, Bay Pines, Florida and University of South Florida.
"Calcium Signaling Deficit" Hypothesis for Alzheimer's Disease.—Updated 10 October 2001
By Ming Chen, VA Medical Center at Bay Pines, Florida.
The "Coblaminergic" Hypothesis—Posted October 2000
By Andrew McCaddon
Dementia as a neocortical disconnection syndrome: morphological and biochemical characterization of the vulnerable neurons
By Dr. Patrick Hof, Mt. Sinai School of Medicine
Alzheimer changes in hypothalamic nuclei: Their relationship to neuronal activity and clinical symptoms
By Dick Swaab and Ahmad Salehi, Netherlands Institute for Brain Research
"Apoptosis in Alzheimer's Disease"—Posted 5 May 1999
Panel discussion on with Paul Coleman, Carl Cotman, Mark Smith, George Perry, Mark Mattson.
"Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down's syndrome patients"—Posted May 1998
By van Leeuwen FW, et al.
"Alzheimer Presenilins in the Nuclear Membrane, Interphase Kinetochores, and Centrosomes Suggest a Role in Chromosome Segregation"—Posted March 1998
By Li JH, Xu M, Zhou H. Ma J. and Potter H.
"Herpes simplex virus type 1 is a risk factor for Alzheimer’s disease"
By Ruth F. Itzhaki, Woan-Ru Lin and Gordon K. Wilcock.
"Towards an animal model of Alzheimer's disease: Can phorbol esters fan the flames?"
By N.R. Smalheiser.
"The cause of neuronal pathology in Alzheimer's disease"
By J.C. Vickers, et al.
"Oxidative Stress Is Central To The Pathogenesis Of Alzheimer Disease"
By M.A. Smith, G. Perry.
"The Role of the Carboxyl-Terminal fragment of APP in the Neurodegeneration and Cognitive Loss in Alzheimer Disease"—Posted September 1997
By Rachael Neve.
"NMDA Receptor Dysfunction And Alzheimer's Disease"—Posted September 1997
By John Olney.
Debate: Multi-Infarct Dementia: Disease Entity or Alzheimer's Lesion?