Alzheimer Disease ; etiology ; Brain Ischemia ; etiology ; Epilepsy ; etiology ; Histamine ; physiology ; Humans ; Parkinson Disease ; etiology

Disturbances in the sleep-wake cycle and circadian rhythms are common symptoms of Alzheimer Disease (AD), and they have generally been considered as late consequences of the neurodegenerative processes. Recent evidence demonstrates that sleep-wake and circadian disruption often occur early in the course of the disease and may even precede the development of cognitive symptoms. Furthermore, the sleep-wake cycle appears to regulate levels of the pathogenic amyloid-beta peptide in the brain, and manipulating sleep can influence AD-related pathology in mouse models via multiple mechanisms. Finally, the circadian clock system, which controls the sleep-wake cycle and other diurnal oscillations in mice and humans, may also have a role in the neurodegenerative process. In this review, we examine the current literature related to the mechanisms by which sleep and circadian rhythms might impact AD pathogenesis, and we discuss potential therapeutic strategies targeting these systems for the prevention of AD.
Alzheimer Disease/*etiology/therapy ; Animals ; *Circadian Rhythm ; Disease Models, Animal ; Humans ; Mice ; *Sleep

OBJECTIVETo observe the correlation between the decline of cognitive function and the level of plasma homocysteine in patients with Alzheimer's disease (AD).

METHODSThirty six AD patients were selected from hospitals in Tianjin. The enrolled patients were in accord with the diagnosis criteria. Thirty two control subjects were corresponding patients without AD in the period. Blood samples were extracted from each subject to determine the levels of homocysteine (Hcy) and folate. Cognitive status was evaluated by the mini- mental state examination (MMSE) and clinical dementia rating scale (CDR).

RESULTSThe mean value of serum Hcy concentration [(17.51 +/- 5.62) micromol/L] of AD group was higher than that of control group [(12.38 +/- 4.25)micromol/L]. The serum [(5.17 +/- 1.76) microg/L] and diet folate [(206.94 +/- 44.51) microg/d] concentration of AD group were lower than those of control group [(7.92 +/- 2.22) microg/L, (259.74 +/- 41.92) microg/ d]. The incidence of hyperhomocysteinemia in AD group (64%) was higher than that in control group (22%). A significant relation between Hcy concentrations and the CDR was observed. With the increase of Hcy concentrations the CDR raised, and with the increase of Hcy concentrations the MMSE decreased.

CONCLUSIONHyperhomocysteinemia is one of the risk factors inducing the onset of AD. There is a significant negative correlation between Hcy levels and cognitive levels in AD group. Folate deficiency is an important reason to cause elevated Hcy levels in AD.

Alzheimer Disease ; blood ; etiology ; Case-Control Studies ; Folic Acid ; blood ; Homocysteine ; blood ; Humans ; Hyperhomocysteinemia ; blood ; complications

Alzheimer Disease ; etiology ; Amyloid ; drug effects ; metabolism ; Clinical Trials as Topic ; Humans ; Models, Theoretical

Our previous studies proposed that Alzheimer's disease (AD) is a metabolic disorder and hypothesized that abnormal brain glucose metabolism inducing multiple pathophysiological cascades contributes to AD pathogenesis. Aging is one of the great significant risk factors for AD. Membrane aging is first prone to affect the function and structure of the brain by impairing glucose metabolism. We presume that risk factors of AD, including genetic factors (e.g., the apolipoprotein E ε4 allele and genetic mutations) and non-genetic factors (such as fat, diabetes, and cardiac failure) accelerate biomembrane aging and lead to the onset and development of the disease. In this review, we further modify our previous hypothesis to demonstrate "membrane aging" as an initial pathogenic factor that results in functional and structural alterations of membranes and, consequently, glucose hypometabolism and multiple pathophysiological cascades.
Aging ; pathology ; Alzheimer Disease ; etiology ; pathology ; Animals ; Brain ; pathology ; Cell Membrane ; pathology ; Humans

Alzheimer disease (AD) is the most common type of dementia characterized by the progressive cognitive and social decline. Clinical drug targets have heavily focused on the amyloid hypothesis, with amyloid beta (Aβ), and tau proteins as key pathophysiologic markers of AD. However, no effective treatment has been developed so far, which prompts researchers to focus on other aspects of AD beyond Aβ, and tau proteins. Additionally, there is a mounting epidemiologic evidence that various environmental factors influence the development of dementia and that dementia etiology is likely heterogenous. In the past decades, new risk factors or potential etiologies have been widely studied. Here, we review several novel epidemiologic and clinical research developments that focus on sleep, hypoxia, diet, gut microbiota, and hearing impairment and their links to AD published in recent years. At the frontiers of AD research, these findings and updates could be worthy of further attention.
Alzheimer Disease/etiology* ; Amyloid ; Amyloid beta-Peptides ; Humans ; Risk Factors ; tau Proteins

Underlying cognitive declines in Alzheimer's disease (AD) are the result of neuron and neuronal process losses due to a wide range of factors. To date, all efforts to develop therapies that target specific AD-related pathways have failed in late-stage human trials. As a result, an emerging consensus in the field is that treatment of AD patients with currently available drug candidates might come too late, likely as a result of significant neuronal loss in the brain. In this regard, cell-replacement therapies, such as human embryonic stem cell- or induced pluripotent stem cell-derived neural cells, hold potential for treating AD patients. With the advent of stem cell technologies and the ability to transform these cells into different types of central nervous system neurons and glial cells, some success in stem cell therapy has been reported in animal models of AD. However, many more steps remain before stem cell therapies will be clinically feasible for AD and related disorders in humans. In this review, we will discuss current research advances in AD pathogenesis and stem cell technologies; additionally, the potential challenges and strategies for using cell-based therapies for AD and related disorders will be discussed.
Alzheimer Disease/etiology/*therapy ; Animals ; Cell- and Tissue-Based Therapy ; Disease Models, Animal ; Humans ; Research ; *Stem Cell Transplantation

Alzheimer's disease (AD) has become one of the most important and most interesting focuses in the field of medical and scientific research. Up to now, the pathogenesis of AD has not been completely clarified. However, the high-density of amyloid β-protein (Aβ) in senile plaques of AD brain and the neurotoxicity of Aβ have been indisputable facts. The mechanisms underlying Aβ neurotoxicity are very complicated, involving calcium overload, inflammation, ion channel dysfunction, oxidative stress and so on. Among all of those, the mechanism of oxidative stress in Aβ neurotoxicity and the experimental progress of antioxidants in AD treatment have been widely reported in recent years. This review mainly discussed current research progresses on the oxidative stress of Aβ, so as to provide readers with some clues to the antioxidant therapy of AD.
Alzheimer Disease ; etiology ; metabolism ; physiopathology ; Amyloid beta-Peptides ; adverse effects ; metabolism ; Animals ; Antioxidants ; pharmacology ; Humans ; Oxidative Stress ; drug effects ; physiology

Alzheimer Disease ; complications ; pathology ; therapy ; Amyloid beta-Peptides ; metabolism ; Humans ; Mitochondria ; physiology ; Mitochondrial Diseases ; etiology ; tau Proteins ; metabolism

Inflammation has been shown to play an important role in the progression of Alzheimer's disease (AD). Recent epidemical study indicates that the incidence of AD in some populations is substantially influenced by the gene polymorphisms of the inflammation mediators. Meanwhile, an ensured risk factor, the ApoE epsilon4 allele is also reported to directly promote inflammation. Accordingly, it appears that an individual genetic background has partly determined his predisposition for AD by the extent of the inflammation response to the chronic stimulus by beta-amyloid peptide (Abeta) deposits and other antigen stressor in the elderly. Hence we present a hypothesis that the inflammation genotypes may contribute to AD susceptibility. This may provide a new orientation both for future identification of individuals at risk and for personalized medication.
Alzheimer Disease ; complications ; genetics ; Apolipoproteins E ; genetics ; Cytokines ; genetics ; metabolism ; Genetic Predisposition to Disease ; Humans ; Immunity, Innate ; Inflammation ; etiology ; genetics ; Risk Factors