Introduction
There is a lack of awareness and understanding of dementia, which is often considered to be a normal part of ageing or a condition for which nothing can be done.
مقدمه
فقدان آگاهی و درک از زوال عقل وجود دارد، که اغلب به عنوان بخشی طبیعی از پیری در نظر گرفته می شود. شرایطی که برای آن هیچ کاری نمی توان انجام داد.
Dementia is declared to be a public health priority by the World Health Organization (WHO). Alzheimer’s disease, which is the most frequent cause of dementia, is indeed an emerging public health problem. Following the estimation of WHO, the total number of patients with dementia worldwide is about 35.6 million and is expected to nearly double every 20 years, to reach around 115.4 million in 2050. The total estimated worldwide cost of dementia is around 604 billion per year.
سازمان بهداشت جهانی (WHO) دمانس را به عنوان یک اولویت بهداشت عمومی اعلام کرده است. بیماری آلزایمر، که شایع ترین علت زوال عقل است، در واقع یک مشکل بهداشت عمومی در حال ظهور است. به دنبال برآورد WHO، تعداد کل بیماران مبتلا به زوال عقل در سراسر جهان حدود ۳۵.۶ میلیون نفر است و پیش بینی می شود که هر ۲۰ سال تقریباً دو برابر شود. به حدود ۱۱۵.۴ میلیون در سال ۲۰۵۰ برسد. کل هزینه تخمینی زوال عقل در سراسر جهان حدود ۶۰۴ میلیارد در سال است.
If the cause of Alzheimer’s disease is not defined, and treatments to delay or prevent the disease are not provided, the world will face an unprecedented health-care problem by the middle of this century.
اگر علت بیماری آلزایمر مشخص نشده باشد و درمان هایی برای به تاخیر انداختن یا پیشگیری از بیماری ارائه نشود، جهان تا اواسط این قرن با یک مشکل بی سابقه مراقبت های بهداشتی مواجه خواهد شد.
Alzheimer’s disease is the most frequent cause of dementia. The early clinical manifestations are subtle short-term memory deficits and anxio-depressive syndrome. During the slow progression of the disease, the intellectual functions progressively disappear and the patients survive in this devastating state of a complete dependence for more than a decade. The duration of the disease from the appearance of the first symptoms until the manifestation of dementia varies between 5 and 20 years.
بیماری آلزایمر شایع ترین علت زوال عقل است. تظاهرات بالینی اولیه ضعف حافظه و سندرم اضطرابی- افسردگی کوتاه مدت هستند. در طول پیشرفت آهسته بیماری، عملکردهای فکری به تدریج ناپدید می شوند و بیماران در این حالت ویرانگر وابستگی کامل، برای بیش از یک دهه زنده می مانند. طول مدت بیماری از ظهور اولین علائم تا تظاهرات زوال عقل بین آن متغیر است ۵ و ۲۰ سال.
The most characteristic pathological hallmarks of Alzheimer’s disease are the accumulation of senile plaques and neurofibrillary tangles and the deposition of beta amyloid and pathologically phosphorylated tau protein in the affected brain. For the definite diagnosis of Alzheimer’s disease the histological confirmation of these characteristic pathological changes are necessary.
مشخص‌ترین علائم پاتولوژیک بیماری آلزایمر تجمع پلاک های پیری و پیچیدگی های عصبی و رسوب بتا آمیلوئید و پروتئین تاو فسفریله پاتولوژیک در ناحیه آسیب دیده مغز برای تشخیص دقیق بیماری آلزایمر، تایید بافتی این پاتولوژیک مشخصه تغییرات لازم است.
All efforts made in research during the last four decades provided important insights into the pathogenesis of Alzheimer’s disease but the cause of the disease is still unclear and the treatment unresolved.
تمام تلاش‌های انجام شده در تحقیقات در طول چهار دهه گذشته بینش های مهمی را در مورد پاتوژنز بیماری آلزایمر ارائه کرده است، اما علت این بیماری هنوز مشخص نیست و درمان مبهم است.
A microbial origin of various chronic inflammatory disorders, including several neurodegenerative, neuropsychiatric and other systemic disorders is strongly intensifying. Accumulating historic and new observations provide evidence of an association between Alzheimer’s disease and infectious agents, and open new opportunities to prevent dementia. Escaping host immune defenses microorganisms are able to initiate and sustain chronic infection and reproduce the pathological and biological hallmarks of Alzheimer’s disease.
منشا میکروبی انواع اختلالات التهابی مزمن، از جمله چندین اختلال عصبی، عصبی روانی و سایر اختلالات سیستمیک به شدت در حال تشدید است. انباشته شدن مشاهدات تاریخی و جدید شواهدی از ارتباط بین بیماری آلزایمر و عوامل عفونی را ارائه می دهد و فرصت های جدیدی را برای جلوگیری از زوال عقل باز می کند. میکروارگانیسم های فرار از دفاع ایمنی میزبان قادر به شروع و حفظ عفونت مزمن و بازتولید علائم پاتولوژیک و بیولوژیکی بیماری آلزایمر هستند.
This handbook assembling and connecting findings with respect to the infectious origin of Alzheimer’s disease is a first attempt to show that the accumulated data provided by hundreds of authors are worth of interest. The amount and the quality of data deserve the attention of the neuroscience community, physicians and health care authorities of governments worldwide. This approach brings new solution to define the cause of Alzheimer’s disease and offer the possibility of a targeted therapy to prevent the disease. It is critical to take the right decisions today and not wait another century for the long awaited cure because the patients are continuously suffering.
این کتابچه راهنمای گردآوری و پیوند یافته‌ها با توجه به منشأ عفونی بیماری آلزایمر، اولین تلاشی است برای نشان دادن اینکه داده‌های انباشته‌شده ارائه شده توسط صدها نویسنده ارزشمند است. مقدار و کیفیت داده ها مستحق توجه جامعه علوم اعصاب، پزشکان و مقامات مراقبت های بهداشتی دولت ها در سراسر جهان است. این رویکرد راه حل جدیدی را برای تعریف علت بیماری آلزایمر و ارائه امکان درمان هدفمند برای پیشگیری از این بیماری به ارمغان می آورد. امروز بسیار مهم است که تصمیمات درست گرفته شود و یک قرن دیگر برای درمان مورد انتظار منتظر نمانیم زیرا بیماران پیوسته در رنج هستند.
The urgent need to explore the role of infectious agents in Alzheimer’s disease is expressed by scientists around the world in the first chapter of the book.
نیاز فوری به کشف نقش عوامل عفونی در بیماری آلزایمر توسط دانشمندان سراسر جهان در فصل اول کتاب بیان شده است.
That chronic inflammation is an important factor in the pathogenesis of Alzheimer’s disease is well established and is summarized in the book by the pioneers of this important field of Alzheimer research.
این که التهاب مزمن عامل مهمی در پاتوژنز بیماری آلزایمر است به خوبی ثابت شده است و توسط پیشگامان این حوزه مهم تحقیقات آلزایمر در کتاب خلاصه شده است.
Recent research demonstrated the involvement of various bacteria in Alzheimer’s disease. Chlamydia pneumoniae, various spirochetes, including Borrelia burgdorferi, and periodontal pathogens, comprising Porphyromonas gingivalis and several periodontal pathogen spirochetes were detected in the brain in Alzheimer’s disease, as reviewed in several chapters of the book. Biofilm formation of spirochetes in senile plaques and the association of polymicrobial periodontal disorders with Alzheimer’s disease are also discussed. The bacterial burden and meta-analysis of bacterial infections in Alzheimer’s disease are also highlighted in two distinct chapters.
تحقیقات اخیر نقش باکتری های مختلف را در بیماری آلزایمر نشان داده است. کلامیدیا پنومونیه، اسپیروکت‌های مختلف، از جمله Borrelia burgdorferi، و پاتوژن‌های پریودنتال، شامل Porphyromonas gingivalis و چندین اسپیروکت پاتوژن پریودنتال در مغز در بیماری آلزایمر شناسایی شدند، همانطور که در چندین فصل از کتاب بررسی شد. تشکیل بیوفیلم اسپیروکت ها در پلاک های پیری و ارتباط اختلالات پریودنتال چند میکروبی با بیماری آلزایمر نیز مورد بحث قرار گرفته است. بار باکتریایی و متاآنالیز عفونت های باکتریایی در بیماری آلزایمر نیز در دو فصل مجزا برجسته شده است.
Viral infections associated with Alzheimer’s disease, including Herpes simplex virus type 1 (HSV1) and the anti-viral properties of B-amyloid peptides are also emphasized. Fungal infections occurring in AD is also revised.
The important role of bacterial amyloid as reviewed by one of the best experts in the field, the dysfunction of the bloodbrain barrier, the role of iron, the long neglected important role of homocysteine as reviewed by its discoverer, the influence of genetic factors, including the role of ApoE4 genotype, and various environmental factors, with respect to the invasion of the brain by pathogens in Alzheimer’s disease, are the subjects of several chapters, which were contributed by pioneer scientists with international notoriety. The role of bacterial lipopolysaccharide (LPS) and the influence of pathogen free conditions on neurodegeneration in a mouse model of Alzheimer’s disease are also discussed.
An infectious origin of Alzheimer’s disease raises many important questions, which need an answer. One of them is related to the polymicrobial involvement of chronic inflammatory disorders. The association of various microorganisms with atherosclerosis, diabetes, several neurodegenerative disorders, including Alzheimer’s disease, undoubtedly occurs. Nevertheless, the clinical, pathological and biological hallmarks of these disorders are distinct. Therefore, to define which microorganisms are able to reproduce the clinical and pathological hallmarks of a given disorder is important as it may influence the diagnosis, treatment and prevention strategies.
This book is the symbol of the effort and courage of all those who contributed to this new emerging field of Alzheimer’s research, whether they participated in this book or not. I am grateful for all contributors of this book for their excellent work, for their generosity and their friendly and enthusiastic collaboration. I fully appreciate the help of the editorial board of the Journal of Alzheimer’s Disease (JAD). Particularly I thank Beth Kumar, Managing Editor of JAD, for her prompt help any time I needed it. I am indebted to Rasjel van der Holst, Associate publisher of JAD, IOS Press, for her interactive, kind, and efficient collaboration that I fully appreciated. They both strongly contributed to the realization of this book. I am also very grateful for all those who participated in the time-consuming review process of the chapters in order to provide an objective and high quality book.
It was a pleasure to collaborate with all those who participated in the realization of this book and to give a helping hand to edit this book on the infectious origin of Alzheimer’s disease, which is based on articles and reviews published in JAD during the last ten years. It is the open-minded approach of the journal, which enabled us to realize this book, which will certainly guide future generation to follow a path, which has been suggested by Oskar Fischer more than a century ago.
The final merit of the realization of this book is due to George Perry, the Editor in Chief of JAD and serial Editor of JAD Handbooks, who initiated and supervised the project, and helped in an accurate, diplomatic and scientific way during all the editorial process. I would like also to remember of Mark Smith previous co-editor of JAD, who I had the chance to know and witness the same open minded approach and courage with respect to this new line of Alzheimer’s research.
It is expected that in the future many other books will appear on this important topic of Alzheimer’s research. Important results are emerging, e.g. from Massachusetts General Hospital and Harvard University, showing that amyloid beta is an antimicrobial peptide, which accumulates in the Alzheimer’s brain in response to invading pathogens. The courage of Robert Moir and Rudolf Tanzi to redirect genetic research to investigate an infectious origin of Alzheimer’s disease is noteworthy. Drexel University also joined this new line of research highlighting the spirochetal origin and biofilm nature of senile plaques and contributing with a chapter to this book. There are many other ongoing research related to this new topic around the world with the participation of many other universities.
We hope that this first book, will contribute to a breakthrough in the history of Alzheimer’s disease showing the right way to solve one of the most devastating disorders of the human being. As predicted by Thomas Lewis, we hope that to follow this path will conduct us to the “End of Alzheimer’s disease” – as stated in the title of his book.
As so nicely expressed by Katherine Bick and Luigi Amaducci in the introductory remarks of their book on Alzheimer’s disease, “it may be our generation’s good fortune to reach the high ground and see answers plainly. Such is our goal.”
Judith Miklossy
