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

Treatment of Alzheimer's Disease with Anti-Homocysteic acid Antibody

Homocysteic acid (HA) may play an important role in Alzhiemer disease (AD) as we previously reported that HA induced accumulation of intraneuronal A[beta]42. In this study, we first analyzed HA levels in a mouse model of AD. 4-month old pre-pathologic 3xTg-AD mice exhibited higher levels of HA in the hippocampus as compared to age-matched nontransgenic, suggesting that HA accumulation may precede both A[beta] and tau pathologies. To further determine the pathogenic role of HA in AD, we treated young 3xTg-AD mice with vitamin B6-deficient food for 3 weeks to induce the production of HA in the brain. Concominantly, mice received either saline or anti-HA antibody intraventricularly using a guide cannula every 3 days. Mice received anti-HA antibody significantly rescued cognitive impairment induced by vitamin B6 deficiency. Pathologically, 3-week treatment with vitamin B-6 deficient food resulted in strong neurodegeneration in the hippocampal CA1 zone and decreased hippocampal volume. In contrast, anti-HA antibody treatment attenuated these pathological changes. Taken together, we conclude that increased brain HA triggers memory impairment whose condition was deteriorated by amyloid and subsequent neurodegeneration and reduction of neurogenesis. Our results indicate a pathogenic role of HA in AD

Treatment of Alzheimer's Disease with Anti-Homocysteic acid Antibody

Homocysteic acid (HA) may play an important role in Alzhiemer disease (AD) as we previously reported that HA induced accumulation of intraneuronal A[beta]42. In this study, we first analyzed HA levels in a mouse model of AD. 4-month old pre-pathologic 3xTg-AD mice exhibited higher levels of HA in the hippocampus as compared to age-matched nontransgenic, suggesting that HA accumulation may precede both A[beta] and tau pathologies. To further determine the pathogenic role of HA in AD, we treated young 3xTg-AD mice with vitamin B6-deficient food for 3 weeks to induce the production of HA in the brain. Concominantly, mice received either saline or anti-HA antibody intraventricularly using a guide cannula every 3 days. Mice received anti-HA antibody significantly rescued cognitive impairment induced by vitamin B6 deficiency. Pathologically, 3-week treatment with vitamin B-6 deficient food resulted in strong neurodegeneration in the hippocampal CA1 zone and decreased hippocampal volume. In contrast, anti-HA antibody treatment attenuated these pathological changes. Taken together, we conclude that increased brain HA triggers memory impairment whose condition was deteriorated by amyloid and subsequent neurodegeneration and reduction of neurogenesis. Our results indicate a pathogenic role of HA in AD

B6 deficient feeding or homocysteic acid induces the earlier Alzheimer's pathological change in normal C57BL male mice

It is the first report that the earlier Alzheimer's pathological changes can be induced in normal C57BL mice, by B6 deficient feeding for 3 month, and this pathological changes 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 pathology in the normal animal. We actually have observed this pathology in normal C57BL male mice

Treatment of Alzheimer's Disease with Anti-Homocysteic Acid Antibody in 3xTg-AD Male Mice

Alzheimer's disease (AD) is an age-associated progressive neurodegenerative disorder with dementia, the exact pathogenic mechanisms of which remain unknown. We previously reported that homocysteic acid (HA) may be one of the pathological biomarkers in the brain with AD and that the increased levels of HA may induce the accumulation of intraneuronal amyloid-beta (Aβ) peptides. In this study, we further investigated the pathological role of HA in a mouse model of AD. Four-month-old prepathological 3xTg-AD mice exhibited higher levels of HA in the hippocampus than did age-matched nontransgenic mice, suggesting that HA accumulation may precede both Aβ and tau pathologies. We then fed 3-month-old 3xTg-AD mice with vitamin B6-deficient food for 3 weeks to increase the HA levels in the brain. Concomitantly, mice received either saline or anti-HA antibody intraventricularly via a guide cannula every 3 days during the course of the B6-deficient diet. We found that mice that received anti-HA antibody significantly resisted cognitive impairment induced by vitamin B6 deficiency and that AD-related pathological changes in their brains was attenuated compared with the saline-injected control group. A similar neuroprotective effect was observed in 12-month-old 3xTg-AD mice that received anti-HA antibody injections while receiving the regular diet. We conclude that increased brain HA triggers memory impairment and that this condition deteriorates with amyloid and leads to subsequent neurodegeneration in mouse models of AD

Treatment of Alzheimer's Disease with Anti-Homocysteic Acid Antibody in 3xTg-AD Male Mice

Alzheimer's disease (AD) is an age-associated progressive neurodegenerative disorder with dementia, the exact pathogenic mechanisms of which remain unknown. We previously reported that homocysteic acid (HA) may be one of the pathological biomarkers in the brain with AD and that the increased levels of HA may induce the accumulation of intraneuronal amyloid-beta (Aβ) peptides. In this study, we further investigated the pathological role of HA in a mouse model of AD. Four-month-old prepathological 3xTg-AD mice exhibited higher levels of HA in the hippocampus than did age-matched nontransgenic mice, suggesting that HA accumulation may precede both Aβ and tau pathologies. We then fed 3-month-old 3xTg-AD mice with vitamin B6-deficient food for 3 weeks to increase the HA levels in the brain. Concomitantly, mice received either saline or anti-HA antibody intraventricularly via a guide cannula every 3 days during the course of the B6-deficient diet. We found that mice that received anti-HA antibody significantly resisted cognitive impairment induced by vitamin B6 deficiency and that AD-related pathological changes in their brains was attenuated compared with the saline-injected control group. A similar neuroprotective effect was observed in 12-month-old 3xTg-AD mice that received anti-HA antibody injections while receiving the regular diet. We conclude that increased brain HA triggers memory impairment and that this condition deteriorates with amyloid and leads to subsequent neurodegeneration in mouse models of AD

Long-Term Memory Test in the Morris Water Maze task.

<p>Non-transgenic mice had an average score of 3 mice each day. Hemizygous transgenic control (hemizygous + B6 deficient) mice had an average score of 3 transgenic control mice each day. Transgenic experimental (hemizygous + B6 deficient + anti-HA antibody) mice had an average score of 3 transgenic experimental mice each day. 3xTg-AD mice were aged 3 months and 3 weeks. Statistically significant difference was observed after 2 trial days between hemizygous + B6 deficient and hemizygous + B6 deficient + antibody (<i>P</i><0.001) and after 3 trial days between hemizygous + B6 deficient and hemizygous + B6 deficient + antibody (<i>P</i><0.05).</p