Abstract. The aim of this review is to propose a Unified Theory of Alzheimers disease UTAD that integrates all key behavioural, genetic and environmental risk factors in a causal chain of etiological and pathogenetic events. It is based on three concepts that emanate from humans evolutionary history 1 The grandmother hypothesis GMH, which explains human longevity due to an evolutionary advantage in reproduction by trans generational transfer of acquired knowledge. Consequently it is argued that mental health at old age must be the default pathway of humans genetic program and not development of AD. Therefore, mechanism like neuronal rejuvenation NRJ and adult hippocampal neurogenesis AHN that still function efficiently even at old age provide the required lifelong ability to memorize personal experiences important for survival. Cumulative evidence from a multitude of experimental and epidemiological studies indicate that behavioural and environmental risk factors, which impair productive AHN, result in reduced episodic memory performance and in reduced psychological resilience. This leads to avoidance of novelty, dysregulation of the hypothalamicpituitaryadrenal HPA axis and cortisol hypersecretion, which drives key pathogenic mechanisms of AD like the accumulation and oligomerization of synaptotoxic amyloid beta, chronic neuroinflammation and neuronal insulin resistance. By applying to AHN the law of the minimum LOM, which defines the basic requirements of biological growth processes, the UTAD explains why and how different lifestyle deficiencies initiate the AD process by impairing AHN and causing dysregulation of the HPA axis, and how environmental and genetic risk factors such as toxins or Apo. Q4UfcjcspE/hqdefault.jpg' alt='Free Download Kangaroo Jack: G`Day, U.S.A.! Free Download Kangaroo Jack: G`Day, U.S.A.! The aim of this review is to propose a Unified Theory of Alzheimers disease UTAD that integrates all key behavioural, genetic and environmental risk. Watch anime movie online and watch cartoon movie online. You can watch movies online for free. You can watch cartoon movies online for free with proper English translation. These screencaps are provided free for noncommercial entertainment and education fan art, blogs, forums, etc. We are not endorsed, sponsored or affiliated with any. Freakazoid is an American animated television series created by Bruce Timm and Paul Dini and developed by Tom Ruegger for the Kids WB programming block of The WB. E4, respectively, turn into disease accelerators under these unnatural conditions. Consequently, the UTAD provides a rational strategy for the prevention of mental decline and a system biological approach for the causal treatment of AD, which might even be curative if the systemic intervention is initiated early enough in the disease process. Hence an individualized system biological treatment of patients with early AD is proposed as a test for the validity of UTAD and outlined in this review. Keywords Unified theory Alzheimers disease UTAD, Grandmother hypothesis GMH, Neuronal rejuvenation NRJ, Adult hippocampal neurogenesis AHN, Law of the minimum LOM, Curative AD therapy, Causal AD prevention. Background. Alzheimers disease AD is characterized by impairment of hippocampal episodic memory performance followed by a progressive decline of cognitive and social capabilities. Since AD is the major cause of cognitive decline and no curative drug has been developed, research worldwide is intense and highly competitive. Epidemiological, biochemical, molecular, genetic and animal studies provide different entry points into the complex disease process, which led to different theories about the aetiology of AD. Starting with age as the main cause and primary risk factor, AD is being explained by the oligomeric amyloid beta A cascade hypothesis, which includes hyperphosphorylated and dysregulated tau 1, the intoxication hypothesis 24, chronic infections 57, microbiome composition 8, neuronal insulin resistance 9, 1. BBB 1. 1, 1. 2, chronic neuroinflammation, due to multiple causes 1. NRJ 1. 4, synaptic failure 1. All of these theories are more or less deeply embedded in the belief that aging per se is the main etiological cause. In fact, the thought that aging per se is the primary cause of AD is so deeply engrained in our thinking and appears in almost every introduction in any scientific paper about AD to be a compulsory statement, which is rarely challenged. But as I will argue, not only are there a number of serious arguments challenging the age is the primary cause dogma, ageing as the overarching cause also hinders the development of a unified theory of AD UTAD, which incorporates all key findings including the long list of well known environmental and behavioural risk factors, hence explaining the aetiology and pathogenesis of this debilitating disease. In fact, the lack of a UTAD continues to limit the development of effective preventive measures and a curative treatment to trial and error. Therapeutic interventions that focus on such singled out mechanisms continue to fail 1. In addition, prevention trials, which rather base their regimen on the correction of more or less arbitrarily selected risk factors than on a complete theory of AD, were so far also limited in their overall success 1. In contrast, the proposed UTAD overcomes our concept of age per se as the major cause for AD, and provides an encompassing explanation of the aetiology and pathogenesis of Alzheimers. It also allows proposing a number of required individual life changing interventions in order to prevent AD with high probability. In addition, the UTAD might provide the logical framework for a curative regimen, as will be outlined at the end of this review. I would like to point out that I have termed the proposed theory UTAD because it presents a systemic neurobiological framework of how all currently known major behavioural, environmental or genetic risk factors individually or in combinations initiate or accelerate the AD process, despite certain caveats that apply for most if not all theories Although I tried to be as comprehensive and exhaustive as possible in my search using key words like for instance AD risk factor, factors inhibiting AHN or neuroinflammation in the Pub. Med database of the National Center for Biotechnology Information, some minor risk factors might have been overlooked, it needs to be seen if they will verify or falsify the UTAD. The same goes for risk factors, which are already acting today but have not been identified yet, or which emanate from future individual lifestyle choices or cultural developments. Conversely, in some categories of risk factors e. Alvin And The Chipmunks: Chip-Wrecked Online English. I purposely listed only examples, since a comprehensive list e. AD process as proposed by the UTAD, would not add to its understanding and therefore go beyond the scope of this review. It is my hope that once the principal concept of the UTAD is accepted, all risk factors that interfere with the neurobiological mechanisms, which, according to the UTAD, are at the centre of AD can be recognized and investigated more efficiently. Last but not least, behavioural risk factors in context of the UTAD might lead to discussions about free will or freedom of action, which would also go beyond the scope of this review. Aging is required but not causal for ADMeasurement of insulin resistance of the hippocampaltemporal lobe by positron emission tomography with 2 deoxy 2 fluorine 1. D glucose integrated with computed tomography FDG PETCT has become, besides amyloid PET diagnostics 1. AD, having predictive value even decades before the first clinical symptoms of AD manifest themselves 2. One may conclude that the development of AD obviously requires time and, therefore, the logical consequence is that the risk of developing AD will increase with age. But correlation does not a priori equal causation. In this case, for a disease requiring time to develop, age might simply be a precondition but not necessarily a cause. If age was indeed the cause of the disease, AD would not only be a natural outcome of human aging but the fight against AD would be a fight against human nature, which is highly difficult to win. But, fortunately, many lines of evidence disagree with this explanation for example see 2. Particularly from a humans life history point of view, if age per se was indeed the main causative risk factor, why was AD essentially unknown around the beginning of the last centuryAccording to a recent estimate, age would have caused approximately 3. USA alone, making the disease very common 3. But a textbook on neurology published in the late 1.