3 December 2003. Is the cycle of life—new lives born even as the old die—to be found in the hippocampus of Alzheimer's patients? A study in this week’s online PNAS suggests just this, and poses the question of whether we could spur newly born neurons to replace those that are degenerating.
At the Buck Institute for Aging Research in Novato, California, David Greenberg, Kunlin Jin, and their colleagues compared AD and non-AD brain tissue for levels of molecules that are expressed in immature neurons. They found that AD hippocampus contains significantly higher expression of doublecortin, polysialylated nerve cell adhesion molecule (PSA-NCAM), neurogenic differentiation factor (NeuroD), and TUC-4.
In particular, they found that expression of doublecortin and TUC-4 was associated with neurons in the proliferative zone of the dentate gyrus and in the ultimate home of these cells—the granule cell layer—as well as in the CA1 region of Ammon’s horn, a principal site of hippocampal pathology in AD.
"These findings suggest that neurogenesis is increased in AD hippocampus, where it may give rise to cells that replace neurons lost in the disease, and that stimulating hippocampal neurogenesis might provide a new treatment strategy," write the authors.
Addressing possible objections, the authors note that it is unlikely they were simply observing the effects of brain atrophy. For example, actin expression was unchanged, whereas levels of the immature neuronal markers varied with disease severity and anatomical location, among other factors.
Another concern is that transgenic models of AD have shown the opposite, namely, a diminution of neurogenesis. Noting that these models all fail to recapitulate AD fully, the authors suggest it will be interesting to test whether more recent models, such as the APP/tau mice, might show increased neurogenesis.—Hakon Heimer.
Jin K, Peel AL, Mao XO, Lin X, Cottrell B, Henshall DC, Greenberg DA. Increased hippocampal neurogenesis in Alzheimer's disease. Proc Natl Acad Sci U S A. 2003 Dec 5 [Epub ahead of print]