Alzheimer’s disease (AD) is the most common cause of dementia among the elderly. With the advent of the aging society, 24.3 million people are estimated to suffer dementia worldwide, increasing to 42.3 million people by 2020 and 81.1 million by 2040 [1
]. The total estimated worldwide costs of dementia are US$604 billion in 2010, and are estimated to increase by 85% to 2030 [3
]. The cost for caring for the increasing number of people with dementia will rise dramatically and thus will be disastrous burden to our societies within upcoming 10–20
years. To address this social issue, clarification of the pathogenic mechanism of AD and development of AD drugs are urgently expected.
Genetic association with putative AD susceptibility genes has been studied and collected as a publicly available database called AlzGene (http://www.alzgene.org/
]. Pathological signaling has been also studied and two core pathological hallmarks of AD, amyloid plaques and neurofibrillary tangles (NFT) accumulation, have been elucidated intensively. However, wealth of this information has become increasingly difficult to follow, much less interpret, and has not been integrated before. Integration of pathway knowledge bridging amyloid plaques and neurofibrillary tangles has been still missing.
Efforts to construct an AD pathway map have been made before, however, these maps are overviews or partial maps of an AD pathway, and are not comprehensive maps. Manual elaboration is still required to construct a comprehensive and accurate map of a particular signaling pathway [5
]. Efforts to manually construct pathway maps of particular signaling, e.g., Toll-like receptor, EGFR, RB/E2F, mTOR signalings, and dendritic cell signaling in response to pathogenes, have been made before [6
In this study, we collected and manually curated over 100 review articles involving in AD, and built an AD pathway map using CellDesigner [11
], a modeling editor for biochemical pathways. AlzPathway is the first comprehensive map of intra, inter and extra cellular signaling pathways of particular disease. AlzPathway now contains 34 canonical pathways such as APP, mitochondrial and apoptosis pathways, which are composed of 1347 species (proteins, complexes, simple moecules, genes, RNAs, ions, degraded products, and phenotypes), 1070 reactions, 129 phenotypes in neuron, brain blood barrier, presynaptic, postsynaptic, astrocyte, and microglial cells and their cellular localizations. Our AlzPathway provides a powerful AD pathway map for deciphering pathogenesis of AD, and it serves as a pathway reference database just as AlzGene for risk-gene reference database. AlzPathway allows us to not only evaluate candidate risk genes listed by GWAS studies, but also analyze omics data including DNA microarray data and RNA-seq data to reveal pathogenesis of AD. Our pathway map will be an indispensable basic resource for both clarification of the pathogenic mechanism of AD and development of AD drug to address social issues caused by AD.