Dissociation of Alzheimer’s morphological pathology from cognitive impairment

We observed the Alzheimer’s morphological pathology, amyloid production induces Alzheimer’s cognitive impairment, was dissociated from the cognitive impairment. The earlier Alzheimer’s pathological changes can be induced in normal C57BL mice, by B6 deficient feeding 4 months with no amyloid, and this cognitive and memory impairments were completely inhibited by anti-homocysteic acid antibody. According to Koch’s postulate, if a pathogen of Alzheimer’s disease is administrated to the normal animal, we would observe the Alzheimer’s cognitive impairment in the normal animal. We actually have observed this cognitive impairment in normal C57BL male mice with no amyloid. From our observations, it is suggested the dissociation of Alzheimer’s morphological pathology may be possible from the cognitive impairment. Introduction Recently our research team has found (1) that anti-homocysteic acid antibody could show the strong cure and preventive effect on 3xTg-AD mice with normal feeding or with vitamin B6 deficient feeding, which was intended to increase homocysteic acid. Homocysteic acid (HA) was already shown to have a neurodegenerative toxicity and its toxicity was increased by the presence of amyloid (2). And HA is well known as an agonist of glutamic acid receptor such as NMDA and metabotropic receptor (3). Our findings show that the pathological process of 3xTg-AD mice was induced by glutamic acid receptor-bound HA. If HA was a real pathogen of Alzheimer’s disease, we can observe the Alzheimer’s pathology (cognitive and memory impairment) in normal animal, when HA is administrated to normal animal. Here we show that vitamin B6 deficient feeding in normal C57BL mice whose age was 4 month-old showed the earlier Alzheimer’s pathological changes such as cognitive and memory impairment with no amyloid. And these earlier Alzheimer’s pathological process were completely inhibited and recovered to normal cognitive ability such as good memory formation by anti-HA antibody. These our findings have submitted the very important dogma for Alzheimer’s pathological process. That is, HA is one of some real pathogens of Alzheimer’s disease according to Koch’s postulate. And amyloid pathology of Alzheimer’s disease is possible dissociated from the cognitive impairment. Methods Vitamin B6 deficient feeding C57BL male mice (n=10), whose age were 4 month-old, were feeding with vitamin B6 deficient food for 4 months. The vitamin B6 deficient food was same as that described in reference (1). Anti-HA antibody Anti-HA antibodies were purchased from MoBiTec Co. (Germany). Polyclonal antisera were raised in rabbits after immunization with a glutaraldehyde-containing HA Nature Precedings : doi:10.1038/npre.2008.2301.2 : Posted 26 Sep 2008 conjugate, following which antibody specificity was determined by performing ELISA