Romberg C, Mattson MP, Mughal MR, Bussey TJ, Saksida LM.
Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept).
J Neurosci. 2011 Mar 2;31(9):3500-7.
PubMed.
I should mention that, of course, I do know Timothy Bussey and Lisa Saksida personally, as they are based at the University of Cambridge, where I work in the Department of Psychiatry. My views on this article are that it is a very exciting and important advance in back translational medicine (1) in that Romberg et al. (2) have developed a mouse model that shows the same form of attentional impairment seen in patients with Alzheimer’s disease. I and my colleagues have shown that this impairment in attention can be improved by treatment with cholinesterase inhibitors (3,4). Indeed, these early results formed the proof-of-concept study for the current symptomatic treatments that are now available for patients with Alzheimer’s disease, including donepezil (Aricept). Romberg et al. have now shown a similar enhancement in performance with donepezil using an "identical" test in mice.
The reason that many "animal models" of diseases such as Alzheimer’s disease have been unsuccessful in identifying new treatments, both symptomatic and neuroprotective, is that they have not reproduced the same cognitive dysfunction seen in the human disorder itself. The ideal animal model should have neurobiology closely aligned to the disease that is being modeled, together with the same symptom profile. This has been very hard to achieve. Romberg et al. now show a model that is closely aligned to the neurobiology and exhibits a prominent symptom of Alzheimer’s disease. This should be a great advantage in leading to new treatment development for Alzheimer’s disease.
A further advance would be in demonstrating that this mouse model also has early episodic memory problems, which are the early symptoms shown by Alzheimer’s patients (5). These memory problems are essential for Alzheimer’s disease early detection, which is crucial to ensure that neuroprotective treatments are given to patients before the damage is done, so that individuals can maintain their mental capital and well-being (6).
See also: Sahakian, B.J. (2011). Benefits and opportunities. Royal Society Brain Waves Project Module 1 Report.
References:
Romberg C, Mattson MP, Mughal MR, Bussey TJ, Saksida LM.
Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept).
J Neurosci. 2011 Mar 2;31(9):3500-7.
PubMed.
Eagger SA, Levy R, Sahakian BJ.
Tacrine in Alzheimer's disease.
Lancet. 1991 Jul 6;338(8758):50-1.
PubMed.
Sahakian BJ, Owen AM, Morant NJ, Eagger SA, Boddington S, Crayton L, Crockford HA, Crooks M, Hill K, Levy R.
Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer's disease: assessment of attentional and mnemonic function using CANTAB.
Psychopharmacology (Berl). 1993;110(4):395-401.
PubMed.
Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R, Philpot M, Robbins TW.
A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease.
Brain. 1988 Jun;111 ( Pt 3):695-718.
PubMed.
Beddington J, Cooper CL, Field J, Goswami U, Huppert FA, Jenkins R, Jones HS, Kirkwood TB, Sahakian BJ, Thomas SM.
The mental wealth of nations.
Nature. 2008 Oct 23;455(7216):1057-60.
PubMed.
Comments
University of Cambridge
I should mention that, of course, I do know Timothy Bussey and Lisa Saksida personally, as they are based at the University of Cambridge, where I work in the Department of Psychiatry. My views on this article are that it is a very exciting and important advance in back translational medicine (1) in that Romberg et al. (2) have developed a mouse model that shows the same form of attentional impairment seen in patients with Alzheimer’s disease. I and my colleagues have shown that this impairment in attention can be improved by treatment with cholinesterase inhibitors (3,4). Indeed, these early results formed the proof-of-concept study for the current symptomatic treatments that are now available for patients with Alzheimer’s disease, including donepezil (Aricept). Romberg et al. have now shown a similar enhancement in performance with donepezil using an "identical" test in mice.
The reason that many "animal models" of diseases such as Alzheimer’s disease have been unsuccessful in identifying new treatments, both symptomatic and neuroprotective, is that they have not reproduced the same cognitive dysfunction seen in the human disorder itself. The ideal animal model should have neurobiology closely aligned to the disease that is being modeled, together with the same symptom profile. This has been very hard to achieve. Romberg et al. now show a model that is closely aligned to the neurobiology and exhibits a prominent symptom of Alzheimer’s disease. This should be a great advantage in leading to new treatment development for Alzheimer’s disease.
A further advance would be in demonstrating that this mouse model also has early episodic memory problems, which are the early symptoms shown by Alzheimer’s patients (5). These memory problems are essential for Alzheimer’s disease early detection, which is crucial to ensure that neuroprotective treatments are given to patients before the damage is done, so that individuals can maintain their mental capital and well-being (6).
See also: Sahakian, B.J. (2011). Benefits and opportunities. Royal Society Brain Waves Project Module 1 Report.
References:
Romberg C, Mattson MP, Mughal MR, Bussey TJ, Saksida LM. Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept). J Neurosci. 2011 Mar 2;31(9):3500-7. PubMed.
Eagger SA, Levy R, Sahakian BJ. Tacrine in Alzheimer's disease. Lancet. 1991 Jul 6;338(8758):50-1. PubMed.
Sahakian BJ, Owen AM, Morant NJ, Eagger SA, Boddington S, Crayton L, Crockford HA, Crooks M, Hill K, Levy R. Further analysis of the cognitive effects of tetrahydroaminoacridine (THA) in Alzheimer's disease: assessment of attentional and mnemonic function using CANTAB. Psychopharmacology (Berl). 1993;110(4):395-401. PubMed.
Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R, Philpot M, Robbins TW. A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. Brain. 1988 Jun;111 ( Pt 3):695-718. PubMed.
Beddington J, Cooper CL, Field J, Goswami U, Huppert FA, Jenkins R, Jones HS, Kirkwood TB, Sahakian BJ, Thomas SM. The mental wealth of nations. Nature. 2008 Oct 23;455(7216):1057-60. PubMed.
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