. Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPSw,Ind) mice. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13363-7. PubMed.

Recommends

Please login to recommend the paper.

Comments

Make a Comment

To make a comment you must login or register.

Comments on Primary Papers and News

  1. This paper is a continuation of a study the authors published in the same journal.

    In their previous paper, they stated that transgenic mice expressing mutant forms of APP (22, 23) or presenilin-1 (41) show impaired, rather than increased, neurogenesis. They further stated that it is impossible to predict whether animal models that may more closely resemble AD may have enhanced neurogenesis, because none of these models fully reproduces the features of familial AD, and the molecular stimulus to neurogenesis in AD is unknown.

    In the current study, they used APPSw/Ind transgenic mice, and indicate that the addition of Indiana mutation to APP produces contradictory results compared to the previous studies. They suggested that synaptic abnormalities, which can be found in this APP transgenic mouse, and further, a defect in glutamatergic transmission, may be the stimulus for neurogenesis. However, these kinds of changes may occur in other types of APP transgenic mice, and it is difficult to explain why enhanced neurogenesis occurred only in the APPSw/Ind transgenic animals.

    Another consideration is that the BrdU positive nuclei indicate only proliferation of cells. Although these are most likely stem cells in normal control brain, it may not be the case under pathological conditions. Namely, glia may proliferate at significant levels in aged APP transgenic mice. Thus, analysis of other stem cell markers or quantification of newly born neurons may be desirable.

    This study may not be conclusive, and further studies are necessary in order to understand stem cell biology under AD pathology.

    View all comments by Kiminobu Sugaya
  2. The concept of AD increasing neurogenesis is extremely interesting, and the proposal that this may be a compensatory response plausible. These findings directly disprove an alternative hypothesis: that the memory deficits of AD are related to the clinical phenomenon of "chemo brain," in which patients undergoing chemotherapy and consequent probable disruption of neurogenesis exhibit memory deficits.