Possible Usefulness of Growth Hormone/Insulin-like Growth Factor-I Axis in Alzheimer’s Disease Treatment

Abstract

Alzheimer's disease (AD) has been traditionally conceptualized as a clinicopathological entity, its definite diagnosis requiring the presence of characteristic pathology together with a dementia clinical picture. The fact that certain AD biomarkers show an acceptable sensitivity and specificity to detect AD pathology has shifted the diagnostic paradigm towards a clinicobiological approach. Neuropathological analysis of AD-affected brains reveals extensive atrophy due to neuronal loss, and accumulation of neurofibrillary tangles and neuritic plaques, surrounded by a tract of neuroinflammation and loss of neurons. Recently, emerging evidence supports the concept that AD is also a disorder of metabolic degeneration. Taken together, the neurochemical changes in the brain from patients with AD indicate multiple disturbances and it seems likely that the changes are secondary to more fundamental changes into the brain. There is a physiological decline of the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis with ageing and the possibility that the GH/ IGF-I axis is involved in cognitive deficits has been recognized for several years. The IGF-I is a potent neurotrophic as well neuroprotective factor found in the brain with a wide range of actions in both central and peripheral nervous system. IGF-I is a critical promoter of brain development and neuronal survival and plays a role in neuronal rescue during degenerative diseases. The investigations of GH releasing stimulation tests especially to GHRH in AD are equivocal and in some cases contradictory. When a cholinesterase inhibitor as rivastigmine, a drug for AD, is acutely administered the area under the curve of the GH response to GHRH doubled, showing that rivastigmine is a powerful drug to enhance GH release. Starting with a more accurate diagnosis not of the clinical syndrome, but of underlying molecular defects, that may eventually lead to a personalized, more effective treatment. Hence, the development of novel therapeutic approaches is urgently needed.

Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Alterations and Had an ApoE 4/3 Genotype

“…The patient will be studied again in the next months to analyze if the positive results obtained with the GH treatment continue. In any case, it has recently been postulated that a treatment with GH could be useful in this neurodegenerative disease [47,48]. …”

The Role of Insulin-Like Growth Factors and Insulin-Like Growth Factor–Binding Proteins in the Nervous System

“…There is sufficient evidence for a specific role of the IGF/insulin system for it to be worth considering as a therapeutic target in AD and other neurodegenerative diseases. 326,327 However, these disorders are characterised by IGF and insulin resistance, and directing therapy towards the endocrine IGF/insulin system are likely to have limited effectiveness. Systemic approaches that increase neurovascular coupling and increase transfer at the blood-brain barriers are worthy of consideration.…”

Growth Hormone: Therapeutic Possibilities—An Overview

“…GH may also be a therapeutic treatment in Parkinson’s disease, in which the dopaminergic regulation of GH is abnormal [ 37 ]. Similarly, GH or IGF-I treatment has been proposed as a possible treatment for Alzheimer’s disease [ 38 , 39 , 40 , 41 ] and other neurodegenerative diseases [ 42 ].…”