, Volume 115, Issue 1, pp 1-4
Date: 20 Nov 2007

Research into neurodegenerative disease: an entangled web of mice and men

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From neurodegenerative phenotype to cause and vice versa

Once clinical entities are established, usually based on their phenotypes, clinicians and researchers try to explain these phenotypes from different points of view, such as pathology, biochemistry, physiology, immunology, etc. This inductive way of explanation has been deemed successful and satisfactory, especially when a single causative agent is identified so that a unified reductionist explanation in a deductive way is possible as has been achieved with infectious diseases. Efforts to explain neurodegenerative disease on the basis of human neuropathology, however, have been hampered because of the intrinsic complexities of the human brain and of disease processes, both of them being responsible for disease-specific temporospatial patterns and cytopathologies.

Recent advance in positional cloning stands out by identifying a genetic abnormality as the single determinant tightly linked to the corresponding phenotype. Once the obser