Commentary Cellscience Reviews Vol.3 No.1 ISSN 1742-8130

Amyloid and NGF: The Cain and Abel of Alzheimer's Disease

Aging is associated with memory loss and a deterioration of brain plasticity. Even though common pathways have been identified in the neuropathology of Alzheimer's disease and normal aging, upstream activators of these pathways had not been identified, and the relationship between, for instance, the amyloid and neurotrophin cascades remains unclear. Costantini and collaborators have shed light upon these complicated relationships by demonstrating a role for the insulin-like growth factor-1 receptor (IGF1-R) in the regulation of the TrkA-p75^NTR switch in both normal aging and in Alzheimer's disease models.

Recently Costantini and collaborators have demonstrated (Costantini et al., 2006) that the age-related neurotrophin receptor switch (the TrkA-p75^NTR switch) is regulated by the insulin-like growth factor-1 receptor (IGF1-R) , which is known as the common regulator of life-span and age-related events such as metabolism and homeostasis within the body (see Butler, 2003 for review). They also found that the TrkA-p75^NTR switch is accompanied by the activation of the second messenger ceramide, which in turn may cause stabilization of beta-site APP cleavage and thus an increased production of amyloid. The findings presented by Costantini et al. raise further questions relating to these converging pathways within the brain. It is not known why these alterations occur with aging, through which intracellular organelles these pathological processes occur, and, finally, what the common downstream results of these pathological events are in vivo and in the human brain. If these questions can be answered, it is possible that successful therapeutic interventions may be developed for both age-associated memory impairment (AAMI) and Alzheimer's disease (AD). In this commentary, the latter two questions will be addressed.

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