This paper presents the interesting finding that immunization of the PDAPP mouse model of AD with the EFRH sequence of Aβ promotes neurogenesis. While many reports using the Aβ immunotherapy approach have focused on more classical AD-type pathological features (Aβ levels, cerebral amyloidosis, gliosis, etc.), this paper suggests that neurogenesis may contribute to the beneficial effects of the Aβ vaccine.
The authors propose that mitigating the effects of AD-type neurotoxicity and cognitive function by restoring the neuronal population may promote recovery from AD. Regarding their results in mice, the authors clearly show increased BrdU+NeuN+ cells in response to EFRH immunization. Further, they show that these cells are also positive for Zif268, a marker of synaptic function. I agree with Dr. Greenberg's comment above that a case for functionality would be much stronger in the presence of positive cognitive/behavioral data. Given the current hot debate over the potential (therapeutic) importance of adult neurogenesis, one wonders whether new neurons could actually take the place (i.e., form meaningful synaptic connections) of dysfunctional, dying, and/or dead neurons in AD. It is important to note that the PDAPP mouse model of AD does not manifest appreciable neuronal loss. If these new neurons are indeed functional, could the authors speculate (or maybe they have data) on how these new neurons are taking over for dysfunctional neurons in the PDAPP mice?
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University of Southern California
This paper presents the interesting finding that immunization of the PDAPP mouse model of AD with the EFRH sequence of Aβ promotes neurogenesis. While many reports using the Aβ immunotherapy approach have focused on more classical AD-type pathological features (Aβ levels, cerebral amyloidosis, gliosis, etc.), this paper suggests that neurogenesis may contribute to the beneficial effects of the Aβ vaccine.
The authors propose that mitigating the effects of AD-type neurotoxicity and cognitive function by restoring the neuronal population may promote recovery from AD. Regarding their results in mice, the authors clearly show increased BrdU+NeuN+ cells in response to EFRH immunization. Further, they show that these cells are also positive for Zif268, a marker of synaptic function. I agree with Dr. Greenberg's comment above that a case for functionality would be much stronger in the presence of positive cognitive/behavioral data. Given the current hot debate over the potential (therapeutic) importance of adult neurogenesis, one wonders whether new neurons could actually take the place (i.e., form meaningful synaptic connections) of dysfunctional, dying, and/or dead neurons in AD. It is important to note that the PDAPP mouse model of AD does not manifest appreciable neuronal loss. If these new neurons are indeed functional, could the authors speculate (or maybe they have data) on how these new neurons are taking over for dysfunctional neurons in the PDAPP mice?
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