Alzheimer Disease: Ohio

Landreth G. · Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA. · J Neuroimmune Pharmacol. · Pubmed #18040837 No free full text.

This publication has no abstract.

Smith MA, Perry G, Pryor WA. · Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. · Free Radic Biol Med. · Pubmed #12031888 No free full text.

This publication has no abstract.

Wang X, Su B, Zheng L, Perry G, Smith MA, Zhu X. · Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA. · J Neurochem. · Pubmed #19393022 links to  free full text

Abstract: Mitochondria play critical roles in neuronal function and almost all aspects of mitochondrial function are altered in Alzheimer neurons. Emerging evidence shows that mitochondria are dynamic organelles that undergo continuous fission and fusion, the balance of which not only controls mitochondrial morphology and number, but also regulates mitochondrial function and distribution. In this review, after a brief overview of the basic mechanisms involved in the regulation of mitochondrial fission and fusion and how mitochondrial dynamics affects mitochondrial function, we will discuss in detail our and others' recent work demonstrating abnormal mitochondrial morphology and distribution in Alzheimer's disease (AD) models and how these abnormalities may contribute to mitochondrial and synaptic dysfunction in AD. We propose that abnormal mitochondrial dynamics plays a key role in causing the dysfunction of mitochondria that ultimately damage AD neurons.

Lee HG, Casadesus G, Zhu X, Castellani RJ, McShea A, Perry G, Petersen RB, Bajic V, Smith MA. · Department of Pathology, Case Western Reserve University, Cleveland, OH, USA. · Neurochem Int. · Pubmed #19114068 No free full text.

Abstract: As one of the earliest pathologic changes, the aberrant re-expression of many cell cycle-related proteins and inappropriate cell cycle control in specific vulnerable neuronal populations in Alzheimer's disease (AD) is emerging as an important component in the pathogenesis leading to AD and other neurodegenerative diseases. These events are clearly representative of a true cell cycle, rather than epiphenomena of other processes since, in AD and other neurodegenerative diseases, there is a true mitotic alteration that leads to DNA replication. While the exact role of cell cycle re-entry is unclear, recent studies using cell culture and animal models strongly support the notion that the dysregulation of cell cycle in neurons leads to the development of AD-related pathology such as hyperphosphorylation of tau and amyloid-beta deposition and ultimately causes neuronal cell death. Importantly, cell cycle re-entry is also evident in mutant amyloid-beta precursor protein and tau transgenic mice and, as in human disease, occurs prior to the development of the pathological hallmarks, neurofibrillary tangles and amyloid-beta plaques. Therefore, the study of aberrant cell cycle regulation in model systems, both cellular and animal, may provide extremely important insights into the pathogenesis of AD and also serve as a means to test novel therapeutic approaches.

Su B, Wang X, Nunomura A, Moreira PI, Lee HG, Perry G, Smith MA, Zhu X. · Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA. · Curr Alzheimer Res. · Pubmed #19075578 No free full text.

Abstract: Multiple lines of evidence demonstrate that oxidative stress is an early event in Alzheimer's disease (AD), occurring prior to cytopathology, and therefore may play a key pathogenic role in AD. Oxidative stress not only temporally precedes the pathological lesions of the disease but also activates cell signaling pathways, which, in turn, contribute to lesion formation and, at the same time, provoke cellular responses such as compensatory upregulation of antioxidant enzymes found in vulnerable neurons in AD. In this review, we provide an overview of the evidence of oxidative stress and compensatory responses that occur in AD, particularly focused on potential sources of oxidative stress and the roles and mechanism of activation of stress-activated protein kinase pathways.

Geldenhuys WJ, Van der Schyf CJ. · Department of Pharmaceutical Sciences, Northeastern Ohio Universities Colleges of Medicine and Pharmacy, Rootstown, OH 44272, USA. · Curr Top Med Chem. · Pubmed #18691131 No free full text.

Abstract: Recently, the serotonin 5-HT(6) receptor has been identified as a drug target for attenuating cognitive deficits associated with Alzheimer's disease (AD). Additionally, this receptor may also play a role in schizophrenia, anxiety and obesity. Reports in the literature suggest that the production of selective antagonists for the 5-HT(6) receptor has increased during the last 10 years, with some compounds currently in clinical trials for the treatment of AD. In this review, we will address the rationale for using 5-HT(6) receptor antagonists in AD, as well as report on current advances in the understanding of the structure-activity relationships required to synthesize 5-HT(6) receptor antagonists.

Landreth G, Jiang Q, Mandrekar S, Heneka M. · Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. · Neurotherapeutics. · Pubmed #18625459 links to  free full text

Abstract: Alzheimer's disease (AD) is characterized by the deposition of beta-amyloid within the brain parenchyma and is accompanied by the impairment of neuronal metabolism and function, leading to extensive neuronal loss. The disease involves the perturbation of synaptic function, energy, and lipid metabolism. The development of amyloid plaques results in the induction of a microglial-mediated inflammatory response. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor whose biological actions are to regulate glucose and lipid metabolism and suppress inflammatory gene expression. Thus, agonists of this receptor represent an attractive therapeutic target for AD. There is now an extensive body of evidence that has demonstrated the efficacy of PPARgamma agonists in ameliorating disease-related pathology and improved learning and memory in animal models of AD. Recent clinical trials of the PPARgamma agonist rosiglitazone have shown significant improvement in memory and cognition in AD patients. Thus, PPARgamma represents an important new therapeutic target in treating AD.

Strober LB, Arnett PA. · Department of Psychiatry & Psychology, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. · Clin Neuropsychol. · Pubmed #18609323 No free full text.

Abstract: Prevalence rates of depression in medically ill elderly people are strikingly high. In particular, the prevalences of depression at any given time in Alzheimer's, Parkinson's, and stroke are as high as 87%, 75%, and 79%, respectively. Proper detection and management of depression in primary care is imperative. The present review examines the risk factors, peculiarities, and etiologies of depression in these populations. We suggest that certain features of depression be considered in assessing depression in these populations and provide guidelines for distinguishing depression from medical, psychosocial, and physical complaints common in elderly people. Additionally, we explore the use of self-report instruments of depression and provide guidelines regarding the specific measures and cutoffs most appropriate for use with these populations. To this end, we hope that readers acquire a greater appreciation for the experience of depression of those suffering from these neurological disorders to aid in their assessment.

Rentz CA. · Alzheimer's Association of Greater Cincinnati, Cincinnati, Ohio, USA. · Nurs Manage. · Pubmed #18536588 No free full text.

This publication has no abstract.

Casadesus G, Rolston RK, Webber KM, Atwood CS, Bowen RL, Perry G, Smith MA. · Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, USA. · Adv Clin Chem. · Pubmed #18429496 No free full text.

Abstract: For decades, Alzheimer's disease (AD) has been linked to aging, gender, and menopause. Not surprisingly, this led most investigators to focus on the role of estrogen. While undoubtedly important, estrogen is unlikely the key determinant of disease pathogenesis. Rather, it appears that estrogen may work in conjunction with a novel determinant of disease pathogenesis, namely gonadotropins. The fact that gonadotropins, specifically luteinizing hormone, play a pivotal role in disease is apparent from significant etiological, epidemiological, and pathological evidences. Moreover, targeting gonadotropins appears to have beneficial actions as a therapeutic regimen.

Marchalant Y, Brothers HM, Wenk GL. · Department of Psychology, The Ohio State University, Columbus, OH 43210, USA. · Biomed Pharmacother. · Pubmed #18400455 links to  free full text

Abstract: Aging often leads to cognitive decline due to neurodegenerative process in the brain. As people live longer, there exists a growing concern linked to long-term, slowly debilitating diseases, such as Alzheimer's disease for which a cure has not yet been found. Recently, the role of neuroinflammation has attracted attention due to its slow onset, chronic nature and its possible role in the development of many different neurodegenerative diseases. In the future, treatment of chronic neuroinflammation may help counteract aspects of neurodegenerative disease. Our recent studies have focused upon the endocannabinoid system for its unique effects on the expression of neuroinflammation. The basis for the manipulation of the endocannabinoid system in the brain in combination with existing treatments for Alzheimer's disease will be discussed in this review.

Harnish SM, Neils-Strunjas J. · Department of Communication Sciences & Disorders, University of Cincinnati, Cincinnati, OH 45267-0379, USA. · Semin Speech Lang. · Pubmed #18348091 No free full text.

Abstract: Decline in semantic memory is a key feature of Alzheimer's disease, and reading and writing performance reflects this loss. The article presents an overview of theoretical reading and spelling models, including definitions of key terminology and controversies surrounding the interaction of semantics and the orthographic lexicon. We review literature supporting a direct lexical nonsemantic route in reading and writing. The reading and writing deficits of Alzheimer's disease are contrasted with those of semantic dementia. Methods of assessing semantic memory in reading and writing are outlined, including administering published tests, word lists, homophones, written confrontation naming, verbal fluency, and written narrative analysis.

Downey D. · Cleveland VA Medical Center, Cleveland, OH, USA. · J Neurosci Nurs. · Pubmed #18330411 No free full text.

Abstract: Although the diagnosis of AD can be devastating, treatment options exist that can slow the disease's progression and allow patients to continue performing ADLs, thereby improving the quality of life for both patient and caregiver. Research is ongoing, and it is estimated by the Alzheimer's Association that finding a treatment that could delay onset by only 5 years could reduce the number of individuals with AD by nearly 50% over the next 50 years (Alzheimer's Association, 2007). Although pharmacotherapy is not yet a cure, it does remain an important part of a total approach to caring for patients and families affected by AD.

de la Torre JC. · Institute of Pathology, Case Western Reserve School of Medicine, Cleveland, Ohio, USA. · Neurodegener Dis. · Pubmed #18322369 No free full text.

Abstract: A large body of evidence indicates that sporadic Alzheimer's disease (AD) is a vascular disorder with neurodegenerative consequences and needs to be treated and managed as such. Epidemiologic studies of vascular risk factors, together with preclinical detection tools for AD are proof of concept that cerebral hypoperfusion is one of the earliest pathological signs in the development of cognitive failure. Vascular risk factors involving heart disease and stroke in the elderly individual who already possesses a dwindling cerebrovascular reserve due to advancing age contribute to further decline in cerebral blood flow (CBF) resulting in unrelenting brain hypoperfusion. Brain hypoperfusion, in turn, can reach a critically attained threshold of cerebral hypoperfusion (CATCH) giving rise to a neuronal energy crisis via reduced ATP synthesis. The ensuing metabolic energy crisis initially carves up ischemic-sensitive neurons in the hippocampus and posterior parietal cortex setting up cognitive meltdown and progressive neurodegenerative and atrophic changes in the brain. Neuronal energy compromise accelerates oxidative stress, excess production of reactive oxygen species, aberrant protein synthesis, ionic membrane pump dysfunction, signal transduction impairment, neurotransmitter failure, abnormal processing of amyloid precursor protein resulting in beta-amyloid deposition and axonal microtubule disruption from tau hyperphosphorylation. The high energy metabolic changes leading to oxidative stress and cellular hypometabolism precede clinical expression of AD. Regional CBF measurements using neuroimaging techniques can predict AD preclinically at the mild cognitive impairment stage or even before any clinical manifestation of dementia is expressed. Clinical diagnostic assessment of elderly persons who could develop or already present with memory complaints can prevent, reverse or slow down AD development. Although pathologic aging is the subject of thousands of studies, the question of why the elderly (and not younger people) succumb to AD has not been adequately addressed. The explanation(s) as to why vascular risk factors, for example, can trigger AD or vascular dementia usually in the elderly and not the young should provide vital clues in the search for a strategically effective dementia treatment. This review offers inductive hypothetical darts relative to that critical question.

Webber KM, Casadesus G, Bowen RL, Perry G, Smith MA. · Department of Pathology, Case Western Reserve University, 2103 Cornell Road, Cleveland, Ohio 44106, USA. · Endocr Metab Immune Disord Drug Targets. · Pubmed #18220951 No free full text.

Abstract: Epidemiological and experimental data supporting a role for luteinizing hormone in Alzheimer disease is accumulating. Paralleling the female predominance for developing Alzheimer disease, luteinizing hormone levels are significantly higher in females as compared to males and luteinizing hormone levels are higher still in individuals who succumb to Alzheimer disease. Importantly, luteinizing hormone, which is capable of modulating cognitive behavior, is not only present in the brain, but also has the highest receptor levels in the hippocampus, a key processor of cognition that is severely deteriorated in Alzheimer disease. These findings, together with data indicating that luteinizing hormone modulates amyloid-beta protein precursor processing in vivo and in vitro, suggests that luteinizing hormone may contribute to Alzheimer disease pathology through an amyloid-dependent mechanism. Indeed, abolishing luteinizing hormone, using a potent gonadotropin-lowering agent, leuprolide acetate, in the amyloid-beta protein precursor transgenic mice improved hippocampally-related cognitive performance and decreased amyloid-beta deposition. These promising findings support the importance of luteinizing hormone in Alzheimer disease and bring to the forefront an alternative, and much needed therapeutic avenue for the treatment of this insidious disease.

Van der Schyf CJ, Mandel S, Geldenhuys WJ, Amit T, Avramovich Y, Zheng H, Fridkin M, Gal S, Weinreb O, Bar Am O, Sagi Y, Youdim MB. · Department of Pharmaceutical Science, Northwestern Ohio Universities College of Pharmacy, Rootstown, OH 44272, USA. · Curr Alzheimer Res. · Pubmed #18220515 No free full text.

Abstract: Traditionally, drug design programs are focused on optimizing the specificity of lead compounds against a carefully selected drug target. Disappointingly, this approach to discover a "magic bullet" drug has not met with the expected success for CNS disorders. Transcriptomics and proteomic profiling of neurodegenerative diseases have indicated that they are poly-etiological in origin and that the processes leading to neuronal death are multifactorial. An emerging concept is the design of drug ligands that modulate multiple drug targets identified for a particular disease. In this review we explore some examples of multifunctional drugs which may be useful in the treatment of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease.

Sharma H, Chandola HM, Singh G, Basisht G. · The Ohio State University Center for Integrative Medicine; College of Medicine, The Ohio State University, Columbus, OH 43210, USA. · J Altern Complement Med. · Pubmed #18166127 No free full text.

Abstract: Ayurveda is a comprehensive natural health care system that originated in India more than 5000 years ago. It is still widely used in India as a system of primary health care, and interest in it is growing worldwide as well. Ayurveda has unique concepts and methodologies to address health care throughout the course of life, from pregnancy and infant care to geriatric disorders. Common spices are utilized, as well as herbs, herbal mixtures, and special preparations known as Rasayanas. Purification procedures known as Panchakarma remove toxins from the physiology. Research has been conducted worldwide on Ayurveda. There are encouraging results for its effectiveness in treating various ailments, including chronic disorders associated with the aging process. Pilot studies presented in this paper were conducted on depression, anxiety, sleep disorders, hypertension, diabetes mellitus, Parkinson's disease, and Alzheimer's disease. These preliminary studies yielded positive results and provide a basis for conducting larger, more rigorous clinical trials. Conducting research that compares Ayurveda's comprehensive treatment approach, Western allopathic treatment, and an integrated approach combining the Ayurvedic and allopathic treatments would shed light on which treatment approach is the most effective for the benefit of the patient.

Jiang Q, Heneka M, Landreth GE. · Department of Neurosciences, Alzheimer Research Laboratory, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA. · CNS Drugs. · Pubmed #18072811 No free full text.

Abstract: Alzheimer's disease is a complex neurodegenerative disorder, with aging, genetic and environmental factors contributing to its development and progression. The complexity of Alzheimer's disease presents substantial challenges for the development of new therapeutic agents. Alzheimer's disease is typified by pathological depositions of beta-amyloid peptides and neurofibrillary tangles within the diseased brain. It has also been demonstrated to be associated with a significant microglia-mediated inflammatory component, dysregulated lipid homeostasis and regional deficits in glucose metabolism within the brain. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a prototypical ligand-activated nuclear receptor that coordinates lipid, glucose and energy metabolism, and is found in elevated levels in the brains of individuals with Alzheimer's disease. A recently appreciated physiological function of this type of receptor is its ability to modulate inflammatory responses. In animal models of Alzheimer's disease, PPARgamma agonist treatment results in the reduction of amyloid plaque burden, reduced inflammation and reversal of disease-related behavioural impairment. In a recent phase II clinical trial, the use of the PPARgamma agonist rosiglitazone was associated with improved cognition and memory in patients with mild to moderate Alzheimer's disease. Thus, PPARgamma may act to modulate multiple pathophysiological mechanisms that contribute to Alzheimer's disease, and represents an attractive therapeutic target for the treatment of the disease.

Webber KM, Perry G, Smith MA, Casadesus G. · Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA. · Clin Med Res. · Pubmed #18056027 links to  free full text

Abstract: Several hypotheses have been proposed that attempt to explain the pathogenesis of Alzheimer Disease (AD) including theories involving senile plaque and neurofibrillary tangle formation, increased oxidative stress, and cell cycle abnormalities, since evidence for each of these pathological phenomena have been well documented in AD. Recent epidemiological and experimental data also support a role for the gonadotropin luteinizing hormone in AD. Paralleling the female predominance for developing AD, luteinizing hormone levels are significantly higher in females as compared to males, and furthermore, luteinizing hormone levels are higher still in individuals who succumb to AD. Luteinizing hormone, which is capable of modulating cognitive behavior, is not only present in the brain, but also has the highest receptor levels in the hippocampus, a key processor of cognition that is severely deteriorated in AD. Furthermore, we recently examined cognitive performance in a well-characterized transgenic mouse that over-expresses luteinizing hormone and found that these animals show decreased cognitive performance when compared to controls. We have also found that abolishing luteinizing hormone in amyloid-beta protein precursor transgenic mice (Tg2576) using a potent gonadotropin-lowering gonadotropin-releasing hormone agonist, leuprolide acetate, resulted in improved hippocampally-related cognitive performance and decreased amyloid-beta deposition. These findings, together with data indicating that luteinizing hormone modulates amyloid-beta protein precursor processing in vivo and in vitro, suggest that luteinizing hormone may contribute to AD pathology through an amyloid-dependent mechanism. These promising findings support the importance of luteinizing hormone in AD and bring to the forefront an alternative, and much needed, therapeutic avenue for the treatment of this insidious disease.

Das UN. · UND Life Sciences, 13800 Fairhill Road #321, Shaker Heights, OH 44120, USA. · Prostaglandins Leukot Essent Fatty Acids. · Pubmed #18054217 No free full text.

Abstract: Low blood folate and raised homocysteine concentrations are associated with poor cognitive function. Folic acid supplementation improves cognitive function. Folic acid enhances the plasma concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). EPA, DHA, and arachidonic acid (AA) are of benefit in dementia and Alzheimer's disease by up-regulating gene expression concerned with neurogenesis, neurotransmission and connectivity, improving endothelial nitric oxide (eNO) generation, enhancing brain acetylcholine levels, and suppressing the production of pro-inflammatory cytokines. EPA, DHA, and AA also form precursors to anti-inflammatory compounds such as lipoxins, resolvins, and neuroprotectin D1 (NPD1) that protect neurons from the cytotoxic action of various noxious stimuli. Furthermore, various neurotrophins and statins enhance the formation of NPD1 and thus, protect neurons from oxidative stress and prevent neuronal apoptosis Folic acid improves eNO generation, enhances plasma levels of EPA/DHA and thus, could augment the formation of NPD1. These results suggest that a combination of EPA, DHA, AA and folic acid could be of significant benefit in dementia, depression, and Alzheimer's disease and improve cognitive function.

Sayre LM, Perry G, Smith MA. · Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106, USA. · Chem Res Toxicol. · Pubmed #18052107 links to  free full text

Abstract: There is increasing awareness of the ubiquitous role of oxidative stress in neurodegenerative disease states. A continuing challenge is to be able to distinguish between oxidative changes that occur early in the disease from those that are secondary manifestations of neuronal degeneration. This perspective highlights the role of oxidative stress in Alzheimer's, Parkinson's, and Huntington's diseases, amyotrophic lateral sclerosis, and multiple sclerosis, neurodegenerative and neuroinflammatory disorders where there is evidence for a primary contribution of oxidative stress in neuronal death, as opposed to other diseases where oxidative stress more likely plays a secondary or by-stander role. We begin with a brief review of the biochemistry of oxidative stress as it relates to mechanisms that lead to cell death, and why the central nervous system is particularly susceptible to such mechanisms. Following a review of oxidative stress involvement in individual disease states, some conclusions are provided as to what further research should hope to accomplish in the field.

Das UN. · UND Life Sciences, Shaker Heights, OH 44120, USA. · Med Sci Monit. · Pubmed #18049445 links to  free full text

Abstract: Plasma levels of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and lipid peroxides are high whereas those of endothelial nitric oxide are low in insulin resistance, obesity, type 2 diabetes mellitus, hypertension, hyperlipidemias, metabolic syndrome X, and Alzheimer's disease suggesting that these diseases are characterized by low-grade systemic inflammation. Recent studies showed that the plasma and tissue activities of enzymes butyrylcholinesterase and acetylcholinesterase are elevated in patients with Alzheimer's disease, and diabetes mellitus, hypertension, insulin resistance, and hyperlipidemia. As a result of this increase in the activities of enzymes acetylcholinesterase and butyrylcholinesterase, the plasma and tissue levels of acetylcholine (ACh) will be low. The "cholinergic anti-inflammatory pathway" mediated by acetylcholine acts by inhibiting the production of tumor necrosis factor, interleukin-1, macrophage migration inhibitory factor, and high mobility group box-1 and suppresses the activation of nuclear factor-kappa B expression. ACh is a neurotransmitter and regulates the levels and activities of serotonin, dopamine and other neuropeptides and thus, modulates both immune response and neurotransmission. Hence, both acetylcholinesterase and butyrylcholinesterase by inactivating acetylcholine may enhance inflammation. This suggests that increased plasma and tissue activities of acetylcholinesterase and butyrylcholinesterase seen in various clinical conditions could serve as a marker of low-grade systemic inflammation.

Wang X, Su B, Perry G, Smith MA, Zhu X. · Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA. · Free Radic Biol Med. · Pubmed #18037122 No free full text.

Abstract: Amyloid-beta has long been implicated in the pathogenesis of Alzheimer disease. The focus was initially on the extracellular fibrillar deposits of amyloid-beta but more recently has shifted to intracellular oligomeric forms of amyloid-beta. Unfortunately, the mechanism(s) by which either extracellular or intracellular amyloid-beta induces neuronal toxicity remains unclear. That said, a number of recent studies indicate that mitochondria might be an important target of amyloid-beta. Neurons rely heavily on mitochondria for energy and it is well established that mitochondrial dysfunction might be an important target of amyloid-beta. Mechanistically, amyloid-beta aggregates in mitochondria to impair function, leading to energy hypometabolism and elevated reactive oxygen species production. Additionally, amyloid-beta affects the balance of mitochondrial fission/fusion and mitochondrial transport, negatively impacting a host of cellular functions of neurons. Here, we review the role that amyloid-beta plays in mitochondrial structure and function of neurons and the importance of this in the pathogenesis of Alzheimer disease.

Lerner AJ, Strauss M, Sami SA. · Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. · Geriatrics. · Pubmed #17999565 No free full text.

Abstract: Apathy has been increasingly recognized as a neuropsychiatric symptom in many neurologic disorders. In this paper, we review the clinical features of apathy in Alzheimer's disease. We also review screening, the differential diagnosis including depression, medical illnesses, and mild cognitive impairment, and treating modalities and issues. It must also be recognized that apathy per se almost never occurs as an isolated syndrome, so it must be viewed in the context of an individual's entire behavioral and cognitive status.

Farooqui AA, Ong WY, Horrocks LA, Chen P, Farooqui T. · Department of Molecular and Cellular Biochemistry, The Ohio State University, 1645 Neil Avenue, Columbus, OH 43210, USA. · Brain Res Rev. · Pubmed #17959252 No free full text.

Abstract: Neural membranes are composed of glycerophospholipids, sphingolipids, cholesterol and proteins. The distribution of these lipids within the neural membrane is not random but organized. Neural membranes contain lipid rafts or microdomains that are enriched in sphingolipids and cholesterol. These rafts act as platforms for the generation of glycerophospholipid-, sphingolipid-, and cholesterol-derived second messengers, lipid mediators that are necessary for normal cellular function. Glycerophospholipid-derived lipid mediators include eicosanoids, docosanoids, lipoxins, and platelet-activating factor. Sphingolipid-derived lipid mediators include ceramides, ceramide 1-phosphates, and sphingosine 1-phosphate. Cholesterol-derived lipid mediators include 24-hydroxycholesterol, 25-hydroxycholesterol, and 7-ketocholesterol. Abnormal signal transduction processes and enhanced production of lipid mediators cause oxidative stress and inflammation. These processes are closely associated with the pathogenesis of acute neural trauma (stroke, spinal cord injury, and head injury) and neurodegenerative diseases such as Alzheimer disease. Statins, the HMG-CoA reductase inhibitors, are effective lipid lowering agents that significantly reduce risk for cardiovascular and cerebrovascular diseases. Beneficial effects of statins in neurological diseases are due to their anti-excitotoxic, antioxidant, and anti-inflammatory properties. Fish oil omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have similar anti-excitotoxic, antioxidant and anti-inflammatory effects in brain tissue. Thus the lipid mediators, resolvins, protectins, and neuroprotectins, derived from eicosapentaenoic acid and docosahexaenoic acid retard neuroinflammation, oxidative stress, and apoptotic cell death in brain tissue. Like statins, ingredients of fish oil inhibit generation of beta-amyloid and provide protection from oxidative stress and inflammatory processes. Collective evidence suggests that antioxidant, anti-inflammatory, and anti-apoptotic properties of statins and fish oil contribute to the clinical efficacy of treating neurological disorders with statins and fish oil. We speculate that there is an overlap between neurochemical events associated with neural cell injury in stroke and neurodegenerative diseases. This commentary compares the neurochemical effects of statins with those of fish oil.