Current Alzheimer research
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A major challenge not yet addressed by current therapeutic interventions for Alzheimer's disease (AD) is the regeneration of lost neurons and neural circuitry to restore cognitive function. Therapies that lead to cessation of the degenerative process still leave the brain riddled with deteriorated neural circuits and reduced neuron number. The discovery of neurogenesis in the adult brain and the regenerative potential of neural stem cells holds the promise for restoration of neural populations and regeneration of neural circuits necessary for cerebral function. ⋯ Results of our in vitro studies coupled with our more recent analyses in the triple transgenic mouse model of AD suggest that APalpha is a promising strategy for promoting neurogenesis in the aged brain and potentially for restoration of neuronal populations in brains recovering from neurodegenerative disease or injury. A brief overview of issues impacting the therapeutic potential of neurogenesis and the factors used to promote neurogenesis in the aging and degenerating brain is presented. Also included is a review of our current research into the neurogenic potential of the small molecule, blood brain barrier penetrating, neurosteroid allopregnanolone (APalpha).
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Comparative Study
Autoimmunity in Alzheimer's disease as evidenced by plasma immunoreactivity against RAGE and Abeta42: complication of diabetes.
Features of autoimmunity have been associated with both Alzheimer's disease (AD) and with diabetes. In both diseases high levels of advanced glycation end products (AGEs) and their receptor (RAGE) have been detected in tissues and in the circulation. In addition high titers of antibodies directed against a RAGE-like peptide occur in the circulation. ⋯ For non-diabetic rats, there was a clear age-dependency regarding the magnitude of the IgG levels. These data support the concept of an interrelationship between diabetes and AD. For both diseases one underlying contributing factor to cytotoxicity could be the development of an autoimmune response triggered by the presence of AGEs and amyloid peptides.
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In western countries, Alzheimer's disease (AD) is the most common form of dementia. In fact, if left uncurbed, the economic cost of caring for AD patients could consume the entire gross national product of the USA by the middle of this century. Until recently, the only available drugs for this condition were cholinergic treatments, which symptomatically enhance cognitive state to some degree, but they were not neuroprotective. ⋯ Besides Alzheimer's disease, memantine is currently in trials for additional neurological disorders, including other forms of dementia, depression, glaucoma, and severe neuropathic pain. A series of second-generation memantine derivatives are currently in development and may prove to have even greater neuroprotective properties than memantine. These second-generation drugs take advantage of the fact that the NMDA receptor has other modulatory sites in addition to its ion channel that potentially could also be used for safe but effective clinical intervention.
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It has long been recognised that Alzheimer's disease (AD) patients present an irreversible decline of cognitive functions as consequence of cell deterioration in the forebrain cholinergic projection system (FCPS), particularly, in a structure called nucleus basalis of Meynert (nbM). The reduction of the number of cholinergic cells in the FCPS disrupts not just its functions and direct connexions but also the modulation of other systems causing interference in several aspects of behavioural performance including arousal, attention, learning and emotion. ⋯ After grafting, these cells have the capacity to migrate to lesioned regions of the brain and differentiate into the necessary type of cells that are lacking in the diseased brain, supplying it with the cell population needed to promote recovery. The present article aims to review the main aspects of Alzheimer's disease and to explore the use of neural stem cells grafts as alternative treatment for the consequent functional deterioration.