Neurotrophic factors in Alzheimer's disease: pathogenesis and therapy

Alzheimer's disease (AD) is a common neurodegenerative disease with a prevalence estimated to reach 115 million by 2050. It is characterized by abnormal extracellular accumulation of amyloid-beta (A beta) peptide and intracellular neurofibrillary tangles (NFTs) that result in neuro-inflammation, synaptic dysfunction, neurotransmitter imbalance, neuronal loss, and dendritic changes. A hypothesis of neurotrophic factor (NTF) involvement in neurodegenerative diseases and their potential as a therapeutic tool has emerged. There are wide information gaps on this topic. However, consistent with this hypothesis, AD may be caused by a deficiency in neurotrophin proteins or receptors expression. In AD brains, an increase in nerve growth factor and a decrease in brain-derived neurotrophic factor in the hippocampus and certain neocortical regions, and a decrease in TrkA in the cortex and nucleus basalis has been observed. Thus, comparative data relating to recent hypotheses addressing NTF content and receptors in experimental animals and human brains, along with their potential roles in the treatment of AD, are discussed in this review.