Alzheimer Disease: Texas

Vega GL, Weiner MF. · The Nutrition and Metabolism Laboratory, Metabolic Unit, Veterans Affairs Medical Center, Dallas, TX 75390, USA. · J Mol Neurosci. · Pubmed #17901546 No free full text.

Abstract: A number of epidemiologic studies suggest an association between plasma total cholesterol and risk for Alzheimer's disease (AD). Additionally, it has been suggested that treatment with statins, drugs that block cholesterol biosynthesis, lower the incidence and prevalence of AD and of vascular dementia. This review provides an overview of cholesterol transport within the central nervous system and the impact of statins on brain cholesterol metabolism in subjects with AD. Brain cholesterol is converted to 24-S-hydroxycholesterol, a reaction catalyzed by CYP46. The oxysterol traverses the blood-brain barrier and is transported to the liver by plasma lipoproteins. The levels of 24-S-hydroxy-cholesterol are a reflection of brain cholesterol turnover. Subjects with AD reportedly have high levels of the oxysterol possibly reflecting neuronal death with release of cell membrane cholesterol. We show gender dimorphism in plasma levels of 24-S-hydroxycholesterol in subjects with AD and significant reductions in plasma levels of the oxysterol during treatment with standard doses of statins (lovastatin, simvastatin, and pravastatin). Polymorphisms of apolipoprotein E and CYP46 do not influence the effect of statins on plasma levels of 24-S-hydroxycholesterol. There were no untoward effects of the standard doses of statin for the duration of treatment. Statins are currently in trial to determine their effect on the course of AD.

Goel A, Kunnumakkara AB, Aggarwal BB. · Gastrointestinal Cancer Research Laboratory, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, TX, United States. · Biochem Pharmacol. · Pubmed #17900536 No free full text.

Abstract: Although turmeric (Curcuma longa; an Indian spice) has been described in Ayurveda, as a treatment for inflammatory diseases and is referred by different names in different cultures, the active principle called curcumin or diferuloylmethane, a yellow pigment present in turmeric (curry powder) has been shown to exhibit numerous activities. Extensive research over the last half century has revealed several important functions of curcumin. It binds to a variety of proteins and inhibits the activity of various kinases. By modulating the activation of various transcription factors, curcumin regulates the expression of inflammatory enzymes, cytokines, adhesion molecules, and cell survival proteins. Curcumin also downregulates cyclin D1, cyclin E and MDM2; and upregulates p21, p27, and p53. Various preclinical cell culture and animal studies suggest that curcumin has potential as an antiproliferative, anti-invasive, and antiangiogenic agent; as a mediator of chemoresistance and radioresistance; as a chemopreventive agent; and as a therapeutic agent in wound healing, diabetes, Alzheimer disease, Parkinson disease, cardiovascular disease, pulmonary disease, and arthritis. Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months. Other clinical trials suggest a potential therapeutic role for curcumin in diseases such as familial adenomatous polyposis, inflammatory bowel disease, ulcerative colitis, colon cancer, pancreatic cancer, hypercholesteremia, atherosclerosis, pancreatitis, psoriasis, chronic anterior uveitis and arthritis. Thus, curcumin, a spice once relegated to the kitchen shelf, has moved into the clinic and may prove to be "Curecumin".

Sohrabji F. · Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center College of Medicine, College Station, TX 77843, USA. · Gene Expr. · Pubmed #17708417 No free full text.

Abstract: Although the effect of estrogen replacement therapy on the incidence of the neurodegenerative disease such as Alzheimer's disease is controversial, experimental studies indicate that estrogen replacement to young adult animals is neuroprotective and that perimenopausal estrogen replacement is associated with a decreased incidence of Alzheimer's disease. Estrogen affects a wide variety of cellular processes that can protect neuronal health. This article considers the disruption of the blood-brain barrier in Alzheimer's disease and forwards the hypothesis that estrogen may preserve neural health by maintaining the integrity of the blood-brain barrier.

Dineley KT. · Department of Neurology, George and Cynthia Mitchell Research Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX 77555-0874, USA. · Front Biosci. · Pubmed #17569627 No free full text.

Abstract: Elevated amyloid-beta peptide (Abeta) and loss of nicotinic acetylcholine receptors (nAChRs) stand prominently in the etiology of Alzheimer's disease (AD). Since the discovery of an Abeta-nAChR interaction, much effort has been expended to understand how this interaction may contribute to normal physiological processes as well as AD. Several researchers have expanded on the initial observation of an Abeta-nAChR interaction to characterize the pertinent factors that confer Abeta sensitivity to nAChRs. Some of which include the following: 1. receptor subunit composition; 2. receptor subunit stoichiometry; 3. regional distribution; 4. presynaptic versus somatic distribution; 5. neuron versus glia expression; 6. in vitro expression system. These aspects of nAChR composition and expression appear to confer the specific functional consequences of Abeta interaction which range from blockade of receptor activation to stimulation of second messenger cascades that provide neuroprotection from Abeta toxicity. This review will discuss the extant literature on the subject in terms of clarifying this apparent dichotomy regarding the consequences of Abeta-nAChR interaction during health and disease.

Singh M. · Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA. · Minerva Endocrinol. · Pubmed #17557035 No free full text.

Abstract: Our understanding of the biology of gonadal steroids has expanded such that we now appreciate that the effects of gonadal steroid hormones, including estradiol and progesterone, extend beyond the strict confines of reproductive function and exert their effects on a wide range of tissue targets including, but not limited to, the bone, the heart and the brain. With respect to the brain, an increasing body of literature supports the protective effects of estradiol and progesterone. However, results from the Women's Health Initiative (WHI) underscored the fact that there may be important caveats to these protective effects and include the choice of hormone used. Here, we describe our current understanding of the neurobiology of progesterone and the synthetic progestin used in most formulations of hormone therapy, medroxyprogesterone acetate, and provide a review of the basic and clinical literature that address the importance of progestins in neuroprotection. In addition, we caution that the effects and mechanisms underlying the neurobiological effects of progestins may not be identical to those seen in non central nervous systems. And though additional research is certainly needed to explore the neurobiology of progesterone and its related progestins more completely, we provide evidence that, at least with respect to the brain, not all progestins are created equal.

Herz J. · Department of Molecular Genetics, UT Southwestern, Dallas, TX 75390, USA. · Neuron. · Pubmed #17296548 No free full text.

This publication has no abstract.

Yoo JH, Valdovinos MG, Williams DC. · Center for Autism and Related Disorders, 3001 Bee Caves Road, Austin, TX 78746, USA. · J Autism Dev Disord. · Pubmed #17221321 No free full text.

Abstract: This review discusses the laboratory and clinical research supporting the rationale for the efficacy of donepezil (Aricept USA) in enhancing cognition in autism, Alzheimer disease, Down syndrome, traumatic brain injury, Attention Deficit Hyperactivity Disorder (ADHD), and schizophrenia. While preliminary animal models have shown effective, human studies exclusive of Alzheimer disease are sparse. Although attention and memory are unlikely a sole operation of the cholinergic system, evidence indicates a promising direction for further examination of this hypothesis in autism. Studies that examine changes in operationally defined behaviors and reliable and valid measure of changes in attention and memory are needed.

Lesser JM, Hughes S. · Geropsychiatry Clinic, University of Texas Medical School, Houston, TX, USA. · Geriatrics. · Pubmed #17184138 No free full text.

Abstract: Approximately 50% to 80% of persons diagnosed with Alzheimer's disease (AD) have some type of behavioral or psychiatric condition (eg, agitation, psychosis, and/or disinhibition). Agitation is defined in the context of restlessness, irritability, and resistiveness. Psychosis is recognized as a disturbance in the perception of objective reality. Disinhibition means a chronic loss of social restraint. In the case of AD, disinhibition can present as aggression, hyperactivity, and socially intrusive behavior. Such conditions can be burdensome for physicians and caregivers to manage. Consequences may include caregiver burnout or illness, patient abuse, and even institutionalization for the patient. Management of behavioral disturbances is no longer primarily handled by psychiatrists, but is now entering the realm of family practice and primary care. This article provides evaluation methods and treatment options for the aforementioned behavioral disturbances.

Rubin CD. · Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8889, USA. · Am J Med Sci. · Pubmed #17170622 No free full text.

Abstract: Alzheimer disease is the most common cause of progressive irreversible intellectual loss in aging humans. The number of individuals and families affected by this disorder will continue to grow as society ages worldwide. Our understanding of the biology, underlying pathophysiology, and diagnosis of Alzheimer disease has greatly expanded over the past few years and much has been published in these areas. This review focuses on the primary care of this disorder and addresses the "now what" question. Topics examined include limiting excess disability, responding to commonly raised questions of family members, pharmacologic and nonpharmacologic therapeutic options, long-term planning, and caregiver issues.

Kishida KT, Klann E. · Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA. · Antioxid Redox Signal. · Pubmed #17115936 No free full text.

Abstract: Increasing evidence suggests that reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, act as necessary signaling molecules in processes underlying cognition. Moreover, ROS have been shown to be necessary in molecular process underlying signal transduction, synaptic plasticity, and memory formation. Research from several laboratories suggests that NADPH oxidase is an important source of superoxide in the brain. Evidence is presented here to show that ROS are in fact important signaling molecules involved in synaptic plasticity and memory formation. Moreover, evidence that the NADPH oxidase complex is a key regulator of ROS generation in synaptic plasticity and memory formation is discussed. Understanding redox signaling in the brain, including the sources and molecular targets of ROS, are important for a full understanding of the signaling pathways that underlie synaptic plasticity and memory. Knowledge of ROS function in the brain also is critical for understanding aging and neurodegenerative diseases of the brain given that several of these disorders, including Alzheimer's disease and Parkinson disease, may be exacerbated by the unregulated generation of ROS.

Sohrabji F, Lewis DK. · Department of Neuroscience and Experimental Therapeutics, TAMU Health Science Center, College Station, TX 77843-1114, USA. · Front Neuroendocrinol. · Pubmed #17069877 links to  free full text

Abstract: Since its' discovery over 20 years ago, BDNF has been shown to play a key role in neuronal survival, in promoting neuronal regeneration following injury, regulating transmitter systems and attenuating neural-immune responses. Estrogen's actions in the young and mature brain, and its role in neurodegenerative diseases in many cases overlaps with those observed for BDNF. Reduced estrogen and BDNF are observed in patients with Parkinson's disease and Alzheimer's disease, while high estrogen levels are a risk factor for development of multiple sclerosis. Estrogen receptors, which transduce the actions of estrogen, colocalize to cells that express BDNF and its receptor trkB, and estrogen further regulates the expression of this neurotrophin system. This review describes the distribution of BDNF and trkB expressing cells in the forebrain, and the roles of estrogen and the BDNF-trkB neurotrophin system in Parkinson's disease, Alzheimer's disease and multiple sclerosis.

Dani JA, Bertrand D. · Department of Neuroscience, Program of Structural & Computational Biology & Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030, USA. · Annu Rev Pharmacol Toxicol. · Pubmed #17009926 No free full text.

Abstract: Subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) are constructed from numerous subunit combinations that compose channel-receptor complexes with varied functional and pharmacological characteristics. Structural and functional diversity and the broad presynaptic, postsynaptic, and nonsynaptic locations of nAChRs underlie their mainly modulatory roles throughout the mammalian brain. Presynaptic and preterminal nicotinic receptors enhance neurotransmitter release, postsynaptic nAChRs contribute a small minority of fast excitatory transmission, and nonsynaptic nAChRs modulate many neurotransmitter systems by influencing neuronal excitability. Nicotinic receptors have roles in development and synaptic plasticity, and nicotinic mechanisms participate in learning, memory, and attention. Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to dysfunctions such as epilepsy, schizophrenia, Parkinson's disease, autism, dementia with Lewy bodies, Alzheimer's disease, and addiction.

Thirumangalakudi L, Samany PG, Owoso A, Wiskar B, Grammas P. · Garrison Institute on Aging and Department of Neuropsychiatry and Behavioral Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA. · J Alzheimers Dis. · Pubmed #16988487 No free full text.

Abstract: Data are emerging to support the idea that mediators of angiogenesis are found in the Alzheimer's disease (AD) brain. The objective of this study is to compare the expression of the angiogenic mediators vascular endothelial growth factor (VEGF), angiopoietin, and matrix metalloproteinases (MMPs) in the microcirculation of AD patients and age-matched controls. Our results indicate that angiopoietin-2 and VEGF are expressed by AD- but not control-derived microvessels. AD-derived microvessels also release higher levels of MMP-2 and MMP-9 compared to controls. The data show that despite high levels of MMP-9, assessed by western blot, MMP-9 activity is not detectable in AD microvessels. In this regard we find high levels of the tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) in AD, but not control vessels. Furthermore, we explore the ability of thrombin, previously shown to be present in AD microvessels, to affect TIMP expression in cultured brain endothelial cells and find that thrombin causes up regulation of TIMP-1. These data show that angiogenic changes occur in the microcirculation of the AD brain and suggest that if these changes are contributory to disease pathogenesis, targeting the abnormal brain endothelial cell would provide a novel therapeutic approach for the treatment of this disease.

Singh M, Dykens JA, Simpkins JW. · Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107, USA. · Exp Biol Med (Maywood). · Pubmed #16636299 links to  free full text

Abstract: Estrogens are gonadal steroid hormones that are present in the circulation of both males and females and that can no longer be considered within the strict confines of reproductive function. In fact, the bone, the cardiovascular system, and extrahypothalamic regions of the brain are now well-established targets of estrogens. Among the numerous aspects of brain function regulated by estrogens are their effects on mood, cognitive function, and neuronal viability. Here, we review the supporting evidence for estrogens as neuroprotective agents and summarize the various mechanisms that may be involved in this effect, focusing particularly on the mitochondria as an important target. On the basis of this evidence, we discuss the clinical applicability of estrogens in treating various age-related disorders, including Alzheimer disease and stroke, and identify the caveats that must be considered.

Shah S, Yu G. · Center for Basic Neuroscience and Department of Cell Biology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. · Mol Interv. · Pubmed #16565469 links to  free full text

Abstract: The accumulation of amyloid-beta peptides in the brain is a major factor of Alzheimer Disease. Central to the production of the amyloid-beta peptides are the proteolytic secretases, which, recently, have been important targets of drug discovery. Newly published results indicate that the sorting protein-related receptor sorLA/LR11 regulates processing and trafficking of the precursor of the amyloid-beta peptides, revealing an alternative target for developing molecular clinical therapeutic compounds for Alzheimer Disease.

Soto C, Estrada L, Castilla J. · George and Cynthia Mitchell Center for Alzheimer's disease and related Neurodegenerative Disorders, Departments of Neurology, University of Texas Medical Branch, Galveston, TX 77555, USA. · Trends Biochem Sci. · Pubmed #16473510 No free full text.

Abstract: Misfolded aggregates present in amyloid fibrils are associated with various diseases known as "protein misfolding" disorders. Among them, prion diseases are unique in that the pathology can be transmitted by an infectious process involving an unprecedented agent known as a "prion". Prions are infectious proteins that can transmit biological information by propagating protein misfolding and aggregation. The molecular mechanism of prion conversion has a striking resemblance to the process of amyloid formation, suggesting that misfolded aggregates have an inherent ability to be transmissible. Intriguing recent data suggest that other protein misfolding disorders might also be transmitted by a prion-like infectious process.

Husain MM, Garrett RK. · University of Texas Southwestern Medical School, Dallas, TX 75390, USA. · Neuroimaging Clin N Am. · Pubmed #16443489 No free full text.

Abstract: The diagnosis of dementia of the Alzheimer's type is defined by criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and the National Institute of Neurologic, Communicative Disorders and Stroke-AD and Related Disorders Association. The latter divides diagnosis into definite, probable, and possible Alzheimer's disease (AD), with definitive diagnosis requiring pathologic confirmation. Both criteria require that other causes of dementia are excluded. A diagnosis of AD can be made with reasonably high accuracy using a combination of clinical criteria, neuropsychologic testing, and conventional CT and MR imaging. There is increasing emphasis on early recognition. Although current therapies produce a mild improvement in symptoms, there are several disease-modifying therapies on the horizon. This article reviews current standards in clinical diagnosis and management.

Colom LV. · Department of Biological Sciences, Center of Biomedical Studies, University of Texas at Brownsville/Texas Southmost College, Brownsville, TX 78520, USA. · J Neurochem. · Pubmed #16405497 No free full text.

Abstract: Information processing and storing by brain networks requires a highly coordinated operation of multiple neuronal groups. The function of septal neurons is to modulate the activity of archicortical (e.g. hippocampal) and neocortical circuits. This modulation is necessary for the development and normal occurrence of rhythmical cortical activities that control the processing of sensory information and memory functions. Damage or degeneration of septal neurons results in abnormal information processing in cortical circuits and consequent brain dysfunction. Septal neurons not only provide the optimal levels of excitatory background to cortical structures, but they may also inhibit the occurrence of abnormal excitability states.

Lovett-Racke AE, Cravens PD, Gocke AR, Racke MK, Stüve O. · Department of Neurology, UT Southwestern Medical Center, Dallas, Tex 75390-9036, USA. · Arch Neurol. · Pubmed #16344338 links to  free full text

This publication has no abstract.

Román GC. · Department of Medicine/Neurology, University of Texas Health Science Center at San Antonio, San Antonio, Tex. 78229-3900, USA. · Cerebrovasc Dis. · Pubmed #16327258 No free full text.

Abstract: Brain injury from ischemic or hemorrhagic cerebrovascular disease (CVD) produces decline in cognitive functions and vascular dementia (VaD). Likewise, CVD may cause VaD from hypoperfusion of susceptible brain areas. CVD may also worsen degenerative dementias such as Alzheimer's disease. Significant advances have been made in the identification and control of risk factors for stroke and cardiovascular disease. The main risk factors for VaD include age, hypertension and absence of antihypertensive medication, diabetes, cigarette smoking, history of cardiovascular disease (coronary heart disease, congestive heart failure, peripheral vascular disease), atrial fibrillation, left ventricular hypertrophy, hyperhomocysteinemia, orthostatic hypotension, cardiac arrhythmias, hyperfibrinogenemia, and sleep apnea. Recently identified risk factors include chronic infection and elevation of C-reactive protein, particularly in patients with diabetes. Evidence from controlled clinical trials strongly suggests that control of vascular risk factors, in particular hypertension, could prevent the development of dementia.

Hao Q, Maret W. · Department of Preventive Medicine & Community Health, University of Texas Medical Branch, Galveston, TX 77555, USA. · J Alzheimers Dis. · Pubmed #16308485 No free full text.

Abstract: Alzheimer's disease is associated with oxidative stress and changes in metal metabolism. Among the essential trace metals, zinc has the greatest number and variety of functions in hundreds of enzymes and thousands of protein domains with different types of zinc finger motifs. Moreover, zinc ions are stored in synaptic vesicles of specialized neurons and released during neuronal activity. Based on this multitude of functions, one would expect that impairment of zinc homeostasis in the brain has far-reaching consequences. In spite of the fact that zinc ions are redox-inert in biology, they have profound effects on redox metabolism. Thus, both zinc deficiency and zinc overload elicit oxidative stress that can lead to the death of nerve cells. These pro-oxidant functions contrast with pro-antioxidant functions in a range of physiological zinc concentrations. Oxidative or nitrosative stress can release zinc from proteins with zinc finger and cluster motifs and re-distribute zinc, thereby changing the functions of the proteins from which it is released and to which it binds. The transduction of redox signals into zinc signals and vice versa affects mitochondrial functions and signaling pathways (NF-kappaB, p53, AP-1) where zinc and the zinc donor/acceptor pair metallothionein/thionein are critically involved in life and death decisions of the cell.

Frederickson CJ, Cuajungco MP, Frederickson CJ. · NeuroBioTex, Inc. & The University of Texas Medical School, Galveston TX 77550, USA. · J Alzheimers Dis. · Pubmed #16308484 No free full text.

Abstract: Prior brain injury is a major risk factor in the development of Alzheimer's disease. This is true for traumatic brain injury, stroke or ischemic brain injury, and (more speculatively) for brain injury resulting from the hypo-perfusion-reperfusion in cardiac arrest or cardiac bypass surgery and even hypo- or hypertension. Here we propose that the release of excess, toxic, "floods" of free zinc into the brain that occurs during and after all excitotoxic brain injury is a key factor that sets the stage for the later development of Alzheimer's disease. Rapid and aggressive administration of zinc buffering compounds to patients suffering brain injury may therefore not only ameliorate the acute injury but might also reduce the risk of subsequent development of Alzheimer's disease.

Román GC, Kalaria RN. · University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA. · Neurobiol Aging. · Pubmed #16300856 No free full text.

Abstract: Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the most common forms of dementia. Cerebrovascular lesions frequently coexist with AD, creating an overlap in the clinical and pathological features of VaD and AD. This review assembles evidence for a role for cholinergic mechanisms in the pathogenesis of VaD, as has been established for AD. We first consider the anatomy and vascularization of the basal forebrain cholinergic neuronal system, emphasizing its susceptibility to the effects of arterial hypertension, sustained hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and consequences of disruption of the cholinergic system in cognition and in control of cerebral blood flow are further discussed. We also summarize preclinical and clinical evidence supporting cholinergic deficits and the use of cholinesterase inhibitors in patients with VaD. We postulate that vascular pathology likely plays a common role in initiating cholinergic neuronal abnormalities in VaD and AD.

Rosenberg RN. · Department of Neurology and the Alzheimer's Disease Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036, USA. · Arch Gen Psychiatry. · Pubmed #16275806 links to  free full text

Abstract: CONTEXT: Alzheimer disease (AD) is a major public health issue with a prediction of 12 million Americans being affected by 2025 from the present 4 million. Molecular and genetic findings have provided significant insights into the roles that amyloid, tau, and apolipoprotein E isoforms have in the causation of AD. A central issue in AD pathogenesis is the amyloid cascade hypothesis. It states that abnormal amyloid processing and accumulation is the primary causative factor of AD and other associated neuropathologic abnormalities are of secondary consequence. It is presented to provide the rationale for novel drug and vaccination therapeutic strategies. Future research directed at prediction and prevention of AD through a genomic and proteomic analysis with identification of multiple polymorphic genes that interact, resulting in increased risk for late-onset AD, are the realistic and ultimate goals. A new approach for drug development is required, one that will emphasize a genomic and proteomic analysis to identify at-risk gene sets whose genetic expression is sufficient to cause late onset, sporadic AD. Prediction and prevention of disease prior to clinical signs and symptoms are the goals. OBJECTIVE: A review and analysis from electronic literature databases and subsequent reference searches of the molecular genetic data. including pertinent genetic mutations and abnormal biochemical findings causal of AD, are cited. The amyloid cascade hypothesis, the contributions of apolipoprotein E, and hyperphosphorylated tau are discussed as to their roles in pathogenesis. Molecular targets for potential drug and vaccination therapies are cited from a critical assessment of the molecular and biomedical data. These data form the basis for rational, target-specific drug and vaccination therapies currently employed and planned for the near future. Phase 2 and 3 clinical trial results of drug and vaccination therapies are cited. CONCLUSIONS: A new approach is needed as current pharmacologic therapy directed at symptomatic relief has proved to be marginally effective. The genomic and proteomic basis of AD will be defined in the near future, and corresponding molecular therapeutic targets will be identified. Genomic neurology has arrived and its application to resolving AD is our best hope.

Roney C, Kulkarni P, Arora V, Antich P, Bonte F, Wu A, Mallikarjuana NN, Manohar S, Liang HF, Kulkarni AR, Sung HW, Sairam M, Aminabhavi TM. · Department of Radiology, Division of Advanced Radiological Sciences, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. · J Control Release. · Pubmed #16246446 No free full text.

Abstract: Alzheimer's disease (AD) is the most common cause of dementia among the elderly, affecting 5% of Americans over age 65, and 20% over age 80. An excess of senile plaques (beta-amyloid protein) and neurofibrillary tangles (tau protein), ventricular enlargement, and cortical atrophy characterizes it. Unfortunately, targeted drug delivery to the central nervous system (CNS), for the therapeutic advancement of neurodegenerative disorders such as Alzheimer's, is complicated by restrictive mechanisms imposed at the blood-brain barrier (BBB). Opsonization by plasma proteins in the systemic circulation is an additional impediment to cerebral drug delivery. This review gives an account of the BBB and discusses the literature on biodegradable polymeric nanoparticles (NPs) with appropriate surface modifications that can deliver drugs of interest beyond the BBB for diagnostic and therapeutic applications in neurological disorders, such as AD. The physicochemical properties of the NPs at different surfactant concentrations, stabilizers, and amyloid-affinity agents could influence the transport mechanism.