Targeting therapy for homocysteic acid in the blood represents a potential recovery treatment for cognition in Alzheimer's disease patients.

Tohru Hasegawa,Wataru Ukai

doi:10.18632/aging.101046

Abstract

At present, we have no reliable means of recovering cognitive impairment in Alzheimer's disease (AD) patients. We hypothesized that homocysteic acid (HA) in the blood might represent one such pathogen that could be excreted into the urine. Since DHA is known to reduce circulating levels of homocysteine, and since exercise attenuates this effect, it follows that supplementation of the diet with DHA, along with increased levels of physical activity, may help to reduce cognitive impairment in AD patients. Our hypothesis was proven to be correct because memory problems in 3xTg- AD mice (a model for AD in which animals develop amyloid pathology), and in a mouse model of familial AD, were recovered following treatment with an anti-HA antibody and not by amyloid treatment. Interestingly, 3xTg-AD mice with amyloid pathology showed increased levels of HA level. This could perhaps be explained by the fact that amyloid precursor protein and/or presenilin increases calcium influx, which could then increase levels of superoxide and consequently increase levels of HA from homocysteine or methionine. Our hypothesis is also partially supported by an open clinical trial of certain dietary supplements that has shown impressive results. Also there are other treatments hypothesis which would be possible for the effective therapies, such as ribonucleoprotein therapy, a β-secretase inhibitor treatment and the metabolic enhancement treatment.

Highlights

Amyloid cascade hypothesis is strong and main stream hypothesis in Alzheimer’s field [1]
Second if the amyloid beta cannot induce a toxic cascade flow by an unknown physiological effect, amyloid pathology will not show any degenerative effect to the neuron and amyloid accumulation will occur in the normal brain
It is known that the amyloid pathology stimulates the calcium influx [7], which stimulate oxygen radical formation [8] to produce homocysteic acid from homocysteine or methionine

Summary

Introduction

Amyloid cascade hypothesis is strong and main stream hypothesis in Alzheimer’s field [1]. Since DHA is known to reduce circulating levels of homocysteine, and since exercise attenuates this effect, it follows that supplementation of the diet with DHA, along with increased levels of physical activity, may help to reduce cognitive impairment in AD patients. Recent big two clinical trials of amyloid beta treatment for Alzheimer’s disease were all failed to recover the cognitive impairment [2,3], it has forced us to reconsider this central hypothesis of amyloid pathogen for Alzheimer’s disease.

Results

Conclusion