Metabolic profiling of Alzheimer's disease brains

Alzheimer’s disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology. A lzheimer’s disease (AD) is a type of dementia that causes problems with memory, thinking and behavior among older people. In the AD brain, two abnormal structures called plaques and tangles have been the prime suspects in the severe depression of metabolic mechanisms, killing important nerve cells and impairing higher brain functions. Recently, various researchers compared a wide range of pathophysiological markers between mutation carriers and non-carriers as a function of the parental age at onset in order to evaluate the cascade of events such as clinical, cognitive, imaging, and biochemical measures in the large international cohort of AD patients 1–6 . In this result, the AD process begins more than 30 years before the clinical onset of dementia and is associated with a series of pathophysiological changes that occur over decades in cerebrospinal fluid (CSF) biomarkers related to plaques of amyloid beta (Ab), tangles of tau protein, brain Ab deposition and brain metabolism as well as progressive cognitive impairment 1,2 . Glucose metabolism in particular declines from the first stage of the disease to the onset of the expected symptoms (230 years) 1,7–10 . Although we still do not know how the AD process begins and/or continues, it appears likely that a simple amyloid cascade hypothesis does not fit with the reality of the neurogenic etiology. Moreover, because the underlying cause of a diagnosis of dementia varies, it is not easy to identify the mechanism and brain regions involved in causing AD. So far as known, it is the key of AD process that this pathology and metabolic mechanisms may be contributed to the distinct cognitive profile in brain. Therefore, it is critical to identify the link between metabolic processes and the disease pathology that causes the distinct cognitive profile and brain lesions of AD patients. AD can be definitively diagnosed after death through definitive examination of senile plaques and fibrillary tangles in several brain regions using staining procedures such as Gallyas-Braak (GB). It would be very useful to be able to correlate metabolic changes in specific regions of the brain with the actual pathological changes that occur in AD. Monitoring various metabolites in the brain will enable the creation of multilateral framework to determine the pathophysiological features and processes of the neurogenic etiology.