A Lead Study on Oxidative Stress-Mediated Dehydroepiandrosterone Formation in Serum: The Biochemical Basis for a Diagnosis of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a progressive, yet irreversible, neurodegenerative disease for which there are limited means for its ante-mortem diagnosis. We previously identified a brain- and cell-specific oxidative stress-mediated mechanism for dehydroepiandrosterone (DHEA) biosynthesis present in rat, bovine, and human brain, independent of the cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17) enzyme activity found in the periphery. This alternative pathway is induced by pro-oxidant agents, such as Fe2+ and amyloid-β peptide. Using brain tissue specimens from control and AD patients we subsequently provided evidence that DHEA is formed in the AD brain by the oxidative stress-mediated metabolism of an unidentified precursor, thus depleting the levels of the precursor present in the blood stream. Here, we tested for the presence of this DHEA precursor in human serum using a simple Fe2+-based reaction and determined the amounts of DHEA formed. A total of 86 subjects were included in this study: 19 male and 20 female AD patients; 18 male and 22 female age-matched controls; and 4 men and 3 women with mild cognitive impairment. Serum oxidation resulted in a dramatic increase of DHEA level in control patients, whereas only a moderate or no increase was observed in the AD patients. The DHEA variation after oxidation correlated with the patients' cognitive and mental status. These results suggest that the comparison of DHEA levels in patient serum before and after oxidation could provide a useful tool to diagnose AD.

Omega-3 fatty acid obtained from Nannochloropsis oceanica cultures grown under low urea protect against Abeta-induced neural damage

“…Abeta25-35 is a toxic Abeta peptide that directly impairs neural function without long-time aggregation (Lesne et al 2006). Oxidative stress generated from Abeta deposits in the brain of AD patients can result in an increase in the generation of free radicals through NOX pathway (Williams and Gooch 2014) and impair the endogenous antioxidant system (Rammouz et al 2011;Townsend and Pratico 2005).…”

Hormonal Markers of Cognitive Impairments in Patients with Primary Cerebral Stroke

“…Clinical studies using DHEA to correct cognitive functions have supported the view that it influences memory [12,17]. DHEA has now been shown to have cerebroprotective effects.…”

“…Experimental studies have identified the following biological effects of DHEAS: improvements in memory; antidepressant activity; avoidance of fear and panic; and reductions in aggression in animals [8,17]. Decreases in the circulating DHEAS level are seen in Alzheimer's disease and other forms of dementia [12,17]. Low DHEA levels have been shown to be associated with impairments to the functioning of the synaptic contacts of neurons and their differentiation [8,13,18].…”

“…This increasingly complex situation defines the search for diagnostic and therapeutic measures to prevent the formation and progression of CI in cerebral stroke. An answer to the question of CI in vascular pathology can only be obtained on the basis of an integral approach [10][11][12][13]. In particular, there is great interest in identifying clinical-biochemical correlates of developing CI.…”

“…Production of this hormone is induced by a variety of changes in neurons. Thus, a cell-specific, oxidation stress-mediated mechanism of DHEA biosynthesis has been demonstrated in the brains of rats, cows, and humans [12]. Degenerative processes, particularly Alzheimer's disease, can significantly reduce this protective mechanism.…”