Three Postulates to Help Identify the Cause of Alzheimer's Disease
- 30 May 2011
- journal article
- research article
- Published by IOS Press in Journal of Alzheimer's Disease
- Vol. 24 (4), 657-668
- https://doi.org/10.3233/JAD-2011-101884
Abstract
Two centuries ago, the German bacteriologist Robert Koch proposed three postulates to support a causal relationship between a specific microbe and an infectious disease. Similarly, three postulates are formulated here to help evaluate hypothetical proposals attempting to explain the pathogenesis of Alzheimer's disease (AD). The first postulate requires that the cause of AD precedes the cognitive decline and neurodegenerative pathology that characterize AD. This rule identifies a primary event from a neuropathological effect generated by the disease process. The second postulate stipulates that interventions aimed at the proposed causal event should prevent or reverse the cognitive and neurodegenerative pathology associated with AD prior to disease onset. This postulate emphasizes prevention or reversal of emerging neurocognitive pathology considerably before AD onset. If the first and second postulate requirements are met, the third postulate follows that interventions targeting the causal event should significantly lower the incidence of AD. For a causal hypothesis to be considered "likely" pathogenic to AD, support from all three postulates is a requisite. The pragmatic potential of the three postulates was applied to seven proposals using evidence-based meta-analysis mainly from randomized controlled trials. Proposals included the amyloid-beta, cell cycle, cholinergic, inflammatory, oxidative stress, tau, and vascular hypotheses. Clinical evidence derived from each proposal formed the basis for an inferential conclusion based on the level of confidence provided by the trial data. The three postulates may challenge or help validate a proposed cause-effect relationship to AD and serve as a useful model for designing more intelligent therapeutic interventions aimed at preventing AD.Keywords
This publication has 38 references indexed in Scilit:
- The relationship between blood pressure and cognitive functionNature Reviews Cardiology, 2010
- Retrograde axonal transport: pathways to cell death?Trends in Neurosciences, 2010
- Mechanisms Underlying Inflammation in NeurodegenerationCell, 2010
- Oxidative damage to RNA: mechanisms, consequences, and diseasesCellular and Molecular Life Sciences, 2010
- Beta-Amyloid Deposition and the Aging BrainNeuropsychology Review, 2009
- Cerebral Blood Flow Response to Functional ActivationJournal of Cerebral Blood Flow & Metabolism, 2009
- Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohortNeurology, 2009
- FDG-PET changes in brain glucose metabolism from normal cognition to pathologically verified Alzheimer’s diseaseEuropean Journal of Nuclear Medicine and Molecular Imaging, 2009
- Alzheimer's disease therapeutic research: the path forwardAlzheimer's Research & Therapy, 2009
- Mechanisms of impaired mitochondrial energy metabolism in acute and chronic neurodegenerative disordersJournal of Neuroscience Research, 2007