What Really Causes Alzheimer’s Disease H D. F AROLD OSTER A free copy of this book is available at www.hdfoster.com. “What really causes AIDS” and “What really causes schizophrenia” also can be downloaded at this website. i © 2004 by Harold D. Foster. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by an means, electronic, mechanical, photocopying, recording, or otherwise, without the written prior permission of the author. ii Dedicated to Grey Friar’s Bobby iii A ’ N UTHOR S OTE This book is written and published to provide information on Alzheimer’s disease. It is sold with the understanding that the publisher and author are not engaged in rendering legal, medi- cal, or other professional services. In addition, this book is not to be used in the diagnosis of any medical condition. If “expert” assistance is desired or required, the services of a competent professional, especially one who is an expert in nutrition, should be sought. Every effort has been made to make this book as complete and accurate as possible. However, there may be mistakes both typographical and in content. Therefore, this text should be used as a general guide and not as the ultimate source of information. Factual matters can be checked by reading the cited literature. This book seeks to stimulate, educate, and entertain. The publisher and the author shall have neither liability nor responsibility to any entity or person with respect to any loss or damage caused, or alleged to be caused, directly or indirectly by the concepts or information contained in this book. Anyone not wishing to be bound by the above may return this volume for a refund of its purchase price. iv A CKNOWLEDGEMENTS The unusual cover of this book is based on the painting “When what who why?” by Keith Loreth. My thanks go to him for giving his permission to use this work of art for this purpose. I would also like to thank Dr. Abram Hoffer and Dr. Joseph Campbell with whom I have spent many pleasant lunches at the University Club discussing orthomolecular medicine in general and nutrition in particular. My gratitude is also ex- pressed to several other people who assisted me in the prepa- ration of this volume. Jill Jahansoozi typed the manuscript. Diane Braithwaite undertook the demanding task of typeset- ting, while cover design was in the expert hands of Ken Josephson. My wife, Sarah, helped proofread several drafts. Their dedication and hard work is acknowledged with thanks. Debt is also acknowledged to the professional staff at Trafford Publishing for their assistance with on-demand manufactur- ing and Internet marketing of this book. v There is a principle which is a bar against all information, which is proof against all argument, and which cannot fail to keep man in everlasting ignorance. That principle is condemnation without investigation. Herbert Spencer (1820-1903) vi W R C A ’ D : HAT EALLY AUSES LZHEIMER S ISEASE A E S N XECUTIVE UMMARY There is currently a global Alzheimer’s pandemic involving tens of millions of victims. In the USA alone, the number of those affected is expected to reach 14 million by 2050.1 This suffer- ing and the financial costs associated with it are unnecessary. Alzheimer’s disease is caused by aluminum and is particularly common in those carrying the APO E4 allele(s), who are more susceptible to this toxic metal because they are less capable than the general population of removing brain beta-amyloid and tau proteins. As a consequence, such individuals are at higher risk of developing Alzheimer’s disease, as these abnor- mal proteins build up in the brain and form neuritic plaques and neurofibrillary tangles. Naturally, this process occurs more often and most rapidly in regions that promote the deposition of beta-amyloid and tau. Such “harmful” environments are those in which drinking water is acidic, high in monomeric alumi- num, and lack magnesium, calcium, and silicic acid. Under these circumstances, aluminum enters the brain and impairs various enzymes, including choline acetyltransferase, calcium/ calmodulin kinase II, alkaline phosphatase, and phospholipase A2. The result of this process is the abnormal brain pathology seen in Alzheimer’s disease patients and the disrupted bio- chemistry associated with it. In an earlier publication,2 I called this explanation of the downward spiral, known as Alzheimer’s disease, Foster’s Multiple Antagonist Hypothesis. Retrogenesis, the loss of abilities in cognition, coordination, behaviour, language, and feeding in the reverse order that they were acquired, occurs in Alzheimer’s disease. This is, in part, because aluminum inhibits at least three membrane- bound enzymes, Na+K+ ATPase, acetylcholinesterase, and, most interestingly, the myelin-specific enzyme 2’3’-cyclic nucleotide vii phosphohydrolase.3 As a result, it can cause rapid thinning of the myelin sheath4 and increase its susceptibility to oxidative stress.5 It seems very likely that these destructive processes are linked to demyelinization and so to associated retrogenesis. The APO E4 allele plays a key role in promoting Alzheimer’s disease because of the inefficiency with which those possess- ing this genetic aberration can remove brain beta-amyloid and tau.6 Genetically, however, there is more to Alzheimer’s disease than the APO E4 gene. To date, four genes have been identi- fied as playing a role in either early- or late-onset Alzheimer’s disease: beta-amyloid precursor protein, presenilin-1, preseni- lin-2, and apolipoprotein E genes.7 Workers have linked most of these variants to familial early-onset Alzheimer’s, but the apolipoprotein E4 allele is a relatively common risk factor for developing late-onset Alzheimer’s disease.8 Considerable progress has been made in interpreting the sig- nificance of such genetic variants. To illustrate, mutations in the presenilin-1 gene seem associated with increased super- oxide production and greater vulnerability to amyloid beta peptide toxicity.9 Interestingly, mutations in the presenilin genes, which are linked to more than 40 percent of all familial Alzheimer’s cases, cause enhanced production of an abnormal form of beta-amyloid precursor protein.10 This protein is longer than normal, aggregates more rapidly, kills neurons in culture more effectively, and precipitates preferentially to form amy- loid plaques. The same elongated protein also is produced as a result of mutations in the gene encoding beta-amyloid pre- cursor protein. The literature suggests, therefore, that the gene variants that predispose to both early- and late-onset Alzheimer’s disease do so because they either increase susceptibility to, or mimic, aluminum-related degenerative processes. That is, the genetic viii mutations involved in promoting the development of Alzheim- er’s disease duplicate some of aluminum’s deleterious impacts on the brain and, in so doing, encourage at least one of the following: the growth of neuritic plaques or neurofibrillary tan- gles, excessive free radical formation, and/or higher neural oxidative stress. Consequently, unfortunate individuals carry- ing any one of the genetic variants are much more likely to develop Alzheimer’s disease, even if they are not exposed to the aluminum excess, or to the vitamin and mineral deficiencies, that are normally associated with its etiology. Alzheimer’s disease incidence appears to be rising faster than the population is aging. Obviously, such an increase cannot be due to any genetic cause. One does not have “epidemics” of genetic diseases, simply because the human genome does not change rapidly enough to trigger them. If, as the evidence strongly hints, Alzheimer’s disease is becoming generally more common, it must be because the “harmful environments” that trigger it are now more widespread. There is no doubt that, globally, soils and water are becoming more acidic and, conse- quently, aluminum more soluble. Throughout the 20th and early 21st centuries, as a result of expanding fossil fuel consump- tion, ever increasing quantities of sulphur and nitrogen were emitted into the atmosphere. Here they were converted into sulphuric and nitric acids, elevating the acidity of subsequent precipitation.11 Such acid rain has caused extensive damage to the environment at local, regional, and even global scales. It has been particularly problematic in northern and central Europe, eastern North America, and eastern China where it has been associated with many health costs.12 Simultaneous- ly, commercial fertilizers have been used with increasing fre- quency. These consist predominantly of nitrogen, phosphorus, and potassium. As a consequence of heavy crop yields, agri- cultural soils have been depleted of several minerals that are important for human health, including calcium and magnesium. ix