Intermittent hypoxia produces Alzheimer disease?

Alzheimer disease (AD) is the most common type of dementia, and the neuropathological hallmarks of AD are depositions of amyloid β protein (Aβ) (senile plaques) and hyperphosphorylated tau (neurofibrillary tangles). Accumulating evidence have indicated that aging is the major risk factor of AD, however, lack of suitable models has complicated studying the relationship between aging and AD. In our recent study [1], we have provide some evidence that intermittent hypoxia treatment (IHT) could be a novel tool compensating for this lack. IHT is well known as an experimental model of sleep-disordered breathing (SDB). SDB is characterized by recurrent arousals from sleep and intermittent hypoxemia. Several clinical studies have suggested the close relationship between SDB and dementia including AD. For example, a recent meta analysis revealed that AD patients have a five times higher chance of presenting with obstructive sleep apnea (the most common form of SDB) than cognitively non-impaired individuals of similar age [2]. Thus we investigated whether IHT could be a model for dementia research. IHT was performed as follows: mice were exposed to a protocol of 1 min of pure N2 injection, in order to reduce the fraction of inspired O2 (FIO2) from 21% to 5%, followed by 2 min of room air injection to increase FIO2 from 5% to 21%. This 3 min cycle was repeated for 8 h each day (from 9:00 am to 5:00 pm). We exposed mice to the protocol for 5 days or 28 days, and subjected their hippocampi for microarray analyses and biochemical analyses. Our major findings are as follows: (1) IHT and aging shared common biological processes. (2) IHT led to an increase in phosphorylated tau. At first, we performed Gene Ontology (GO)-based microarray analyses that was previously established by Dr. Hirasawa and his colleagues [3]. We included data derived from mice reared for 12 months (referred to “aging”). Our experimental data were compared with the various other data published in Gene Expression Omnibus (The National Center for Biotechnology Information), and hierarchical clustering was performed to calculate the linkage distances among the experimental data. Interestingly, we revealed Editorial