Neurotrophins - From Pathophysiology to Treatment in Alzheimers Disease

Rainer      Hellweg; Olaf      Schulte-Herbruggen; Maria   C.   Jockers-Scherubl

Abstract

Alzheimers disease (AD) is the most common diagnosis among dementia. As increasing longevity results in larger numbers of AD patients and thus rising economic costs, there has been intense research about the pathophysiology and treatment strategies during the last years. Since neurotrophic factors are not only responsible for neuronal development but also critical for the maintenance of neurons, they represent mediators of high interest within the research of neurodegeneration. Thereby, NGF has been identified as a dynamic pattern during the time course of neurodegeneration in AD. Post mortem studies point to a lack of NGF action in early stages of AD. In contrast NGF is found in enhanced concentrations in brains with severe AD partly due to a pathologically altered axonal transport of NGF in the neurons. Therefore, pharmacological interventions starategies focus on an neurotrophin substitution in mild to moderate cases of AD. Intensive research mostly in rodents has recently led to first promising clinical trials of intracerebral neurotrophin application pointing to a growing role of neurotrophins in the establishment of new pharmacological strategies concerning AD.

Keywords: Cholinergic system, neurotrophins, Alzheimer's disease, basal forebrain, NGF, BDNF

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