Is aging part of Alzheimer's disease, or is Alzheimer's disease part of aging?
ABSTRACT For 70 years after Alois Alzheimer described a disorder of tangle-and-plaque dementia, Alzheimer's disease was a condition of the relatively young. Definitions of Alzheimer's disease (AD) have, however, changed over the past 30 years and under the revised view AD has truly become an age-related disease. Most now diagnosed with AD are elderly and would not have been diagnosed with AD as originally conceived. Accordingly, younger patients that qualify for a diagnosis of AD under both original and current Alzheimer's disease constructs now represent an exceptionally small percentage of the diagnosed population. The question of whether pathogenesis of the "early" and "late" onset cases is similar enough to qualify as a single disease was previously raised although not conclusively settled. Interestingly, debate on this issue has not kept pace with advancing knowledge about the molecular, biochemical and clinical underpinnings of tangle-and-plaque dementias. Since the question of whether both forms of AD share a common pathogenesis could profoundly impact diagnostic and treatment development efforts, it seems worthwhile to revisit this debate.
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ABSTRACT: BACKGROUND: The theory of retrogenesis refers to changes in psychomotor abilities that occur in the reverse order in which they are acquired in normal psychomotor development. Such changes occur along the aging process and are also illustrated by the degenerative changes that occur in Alzheimer's disease (AD). OBJECTIVES: To review the concept of retrogenesis in aging and in AD and to discuss the articles published on the subject in the last ten years. METHODS: A search was conducted in the databases PubMed (MEDLINE), Lilacs, Cochrane and SciELO with the keywords "retrogenesis", "elderly" and "Alzheimer's disease". RESULTS: The literature search resulted in six articles, two of which recently published. We conducted a descriptive analysis of them. We observed that the study of retrogenesis in old age has been done primarily on the basis of AD, mainly through literature reviews and theoretical explorations. These works correlate events observed in AD with some physiological changes, following the opposite direction to the normal development of human beings. DISCUSSION: Based on available literature, we support the notion that functional retrogenesis model illustrate the changes that occur in patients with AD. This notion is supported by experimental models using diffusion tensor imaging and addressing white-matter changes that occur along the aging and the disease processes.Revista de Psiquiatria Clínica 12/2009; 37(3):131-137. · 0.89 Impact Factor
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ABSTRACT: Epidemiological and biochemical studies show that the sporadic forms of Alzheimer's disease (AD) are characterized by the following hallmarks: (a) An exponential increase with age; (b) Selective neuronal vulnerability; (c) Inverse cancer comorbidity. The present article appeals to these hallmarks to evaluate and contrast two competing models of AD: the amyloid hypothesis (a neuron-centric mechanism) and the Inverse Warburg hypothesis (a neuron-astrocytic mechanism). We show that these three hallmarks of AD conflict with the amyloid hypothesis, but are consistent with the Inverse Warburg hypothesis, a bioenergetic model which postulates that AD is the result of a cascade of three events-mitochondrial dysregulation, metabolic reprogramming (the Inverse Warburg effect), and natural selection. We also provide an explanation for the failures of the clinical trials based on amyloid immunization, and we propose a new class of therapeutic strategies consistent with the neuroenergetic selection model.Frontiers in physiology. 01/2014; 5:522.
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ABSTRACT: We report findings from an autopsy of a male in his 40s who died of a brain stem hemorrhage associated with cerebral amyloid angiopathy (CAA), senile plaques (SPs) and neurofibrillary tangles (NFTs), which are histopathological changes associated with Alzheimer’s disease (AD). Our immunohistochemical study demonstrated amyloid β (Aβ) deposition in the small cerebral arteries and SPs. Although hypertension (178/132 mmHg) was detected, the subject was not treated accordingly. CAA coupled with hypertension might have caused the intracerebral hemorrhage (ICH).Legal Medicine 03/2014; · 1.44 Impact Factor