Yang Y, Mufson EJ, Herrup K.
Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease.
J Neurosci. 2003 Apr 1;23(7):2557-63.
PubMed.
This paper stands apart from amongst the swath of papers that describe changes in AD brain as a means of delineating the progressive neurodegenerative mechanism operating in the disease. It is a beautiful example of how a fairly simple and straightforward technical approach can translate into priceless information if combined with careful inquisition, evaluation, and insight. The study explores cases of mild cognitive impairment (MCI) as a precursor to AD. Previous evidence suggests that not all cases of MCI may develop AD, but may evolve into other neurological conditions. The presence of cell cycle markers in every one of the 10 MCI cases studied signifies a role for a cell cycle-driven process, not only in AD, but in other age-associated dementias, as well.
Taken together with the positive results in many different neuronal populations, this study arrives at the conclusion that ectopic reentrance into the cell cycle is a "unified" mechanism of neurodegeneration, indicative of a "single disease process" in all neurons in many disease states. The presence of cell cycle markers in neurons may, therefore, constitute one of the most reliable harbingers of death. The estimation of the duration of this death mechanism in neurons, based on the number of neurons affected, is intriguing in light of practical approaches for intervening with disease. Undoubtedly, the findings presented here need to be substantiated by examining many more cases, but even if wrong, this is an elegant contribution to the scientific literature.
Comments
This paper stands apart from amongst the swath of papers that describe changes in AD brain as a means of delineating the progressive neurodegenerative mechanism operating in the disease. It is a beautiful example of how a fairly simple and straightforward technical approach can translate into priceless information if combined with careful inquisition, evaluation, and insight. The study explores cases of mild cognitive impairment (MCI) as a precursor to AD. Previous evidence suggests that not all cases of MCI may develop AD, but may evolve into other neurological conditions. The presence of cell cycle markers in every one of the 10 MCI cases studied signifies a role for a cell cycle-driven process, not only in AD, but in other age-associated dementias, as well.
Taken together with the positive results in many different neuronal populations, this study arrives at the conclusion that ectopic reentrance into the cell cycle is a "unified" mechanism of neurodegeneration, indicative of a "single disease process" in all neurons in many disease states. The presence of cell cycle markers in neurons may, therefore, constitute one of the most reliable harbingers of death. The estimation of the duration of this death mechanism in neurons, based on the number of neurons affected, is intriguing in light of practical approaches for intervening with disease. Undoubtedly, the findings presented here need to be substantiated by examining many more cases, but even if wrong, this is an elegant contribution to the scientific literature.
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