Homocysteic Acid Mediates Amyloid Pathogenicity for Cognitive Impairment in Alzheimer’s Disease

Recently Alzheimer's Disease Neuroimaging Initiative (ADNI) observation has reported that MCI who has higher level of amyloid decline his cognitive ability faster than MCI who has a relative lower amyloid in his brain. However, in a normal patient's brain in which the amyloid level was almost equal to that of an MCI patient's brain, the cognitive ability was not at all declined. Consequently, a strong debate surrounds the differences between the normal, MCI, and AD patient's brains regarding amyloid toxicity. It is rational that MCI has some unknown factors in which the toxicity is increased in the presence of amyloid, but a normal patient's brain has no such unknown factors. Moreover, we observed that the neurodegenerative effect of homocysteic acid (HA) was significantly higher in MCI than that in a normal patient's brain, and this HA toxicity was enhanced in the presence of amyloid. Therefore, it is highly possible that the previously mentioned unknown factor is HA. The amyloid hypothesis is a legitimate pathogenic theory in AD, but some modification is required to elucidate the human AD process. Moreover, a novel pathogen containing HA can modify this amyloid hypothesis. Therefore, amyloid induces phosphorylated-tau toxicity by HA, and consequently, amyloid induces the neurodegeneration of AD. HA can induce neurodegeneration without the presence of amyloid, and AD without amyloid can be induced by HA.