Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All mutations known to cause familial Alzheimer's disease (AD) act by increasing the levels of soluble beta-amyloid peptide (A beta), especially the longer form, A beta42. However, in vivo elevation of soluble A beta in sporadic AD has so far not been shown. In the present study, we used enzyme-linked immunosorbent assays specific for A beta42 and A beta40 to investigate cerebrospinal fluid from sporadic AD at different stages of disease severity, to clarify the roles of A beta42 and A beta40 during disease progression. We also evaluated three other groups--one group of patients with mild cognitive impairment who were at risk of developing dementia, a cognitively intact, nondemented reference group diagnosed with depression, and a perfectly healthy control group. We found that A beta42 is strongly elevated in early and mid stages of AD, and thereafter it declines with disease progression. On the contrary, A beta40 levels were decreased in early and mid stages of AD. The group of cognitively impaired patients and the depression reference group had significantly higher levels of A beta42 than the healthy control group, implying that A beta42 is increased not only in AD, but in other central nervous system conditions as well. Our data also point out the importance of having thoroughly examined control material. The initial increase and subsequent decrease of A beta42 adds a new biochemical tool to follow the progression of AD and might be important in the monitoring of therapeutics.
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PMID:Cerebrospinal fluid A beta42 is increased early in sporadic Alzheimer's disease and declines with disease progression. 1021 75

Abnormal processing of amyloid precursor protein (APP), in particular the generation of beta-amyloid (Abeta) peptides, has been implicated in the pathogenesis of Alzheimer's disease. This study examined the consequences of deleting the APP gene on hippocampal synaptic plasticity, and upon the biophysical properties of morphologically identified neurones in APP-null mice. The hippocampus of APP-null mice had a characteristic increase in gliosis throughout the CA1 region and a disruption of staining for the dendritic marker MAP2 and the presynaptic marker synaptophysin. The disruption of MAP2 staining was associated with a significant reduction in overall dendritic length and projection depth of biocytin labeled CA1 neurones. In two groups of APP-null mice that were examined at 8-12 months, and 20-24 months of age, there was an impairment in the formation of long-term potentiation (LTP) in the CA1 region compared to isogenic age matched controls. This LTP deficit was not associated with an alteration in the amplitude of EPSPs at low stimulus frequencies (0.033 Hz) or facilitation during a 100 Hz stimulus train, but was associated with a reduction in post-tetanic potentiation. Paired-pulse depression of GABA-mediated inhibitory post-synaptic currents was also attenuated in APP-null mice. These data demonstrate that the impaired synaptic plasticity in APP deficient mice is associated with abnormal neuronal morphology and synaptic function within the hippocampus.
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PMID:Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. 1021 73

The biological roles of nitric oxide (NO) and cGMP as inter- and intracellular messengers have been intensively investigated during the last decade. NO and cGMP both mediate physiological effects in the cardiovascular, endocrinological, and immunological systems as well as in central nervous system (CNS). In the CNS, activation of the N-methyl-D-aspartic acid (NMDA) type of glutamatergic receptor induces Ca(2+)-dependent NOS and NO release, which then activates soluble guanylate cyclase for the synthesis of cGMP. Both compounds appear to be important mediators in long-term potentiation and long-term depression, and thus may play important roles in the mechanisms of learning and memory. Aging and the accumulation of amyloid beta (A beta) peptides are important risk factors for the impairment of memory and development of dementia. In these studies, the mechanism of basal- and NMDA receptor-mediated cGMP formation in different parts of adult and aged brains was evaluated. The relative activity of the NO cascade was determined by assay of NOS and guanylate cyclase activities. In addition, the effect of the neurotoxic fragment 25-35 of A beta (A beta) peptide on basal and NMDA receptor-mediated NOS activity was investigated. The studies were carried out using slices of hippocampus, brain cortex, and cerebellum from 3- and 28-mo-old rats. Aging coincided with a decrease in the basal level of cGMP as a consequence of a more active degradation of cGMP by a phosphodiesterase in the aged brain as compared to the adult brain. Moreover, a loss of the NMDA receptor-stimulated enhancement of the cGMP level determined in the presence of cGMP-phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) was observed in hippocampus and cerebellum of aged rats. However, this NMDA receptor response was preserved in aged brain cerebral cortex. A significant enhancement of the basal activity of NOS by about 175 and 160% in hippocampus and cerebellum, respectively, of aged brain may be involved in the alteration of the NMDA receptor response. The neurotoxic fragment of A beta, peptide 25-35, decreased significantly the NMDA receptor-mediated calcium, and calmodulim-dependent NO synthesis that may then be responsible for disturbances of the NO and cGMP signaling pathway. We concluded that cGMP-dependent signal transduction in hippocampus and cerebellum may become insufficient in senescent brain and may have functional consequences in disturbances of learning and memory processes. A beta peptide accumulated during brain aging and in Alzheimer disease may be an important factor in decreasing the NO-dependent signal transduction mediated by NMDA receptors.
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PMID:Aging modulates nitric oxide synthesis and cGMP levels in hippocampus and cerebellum. Effects of amyloid beta peptide. 1034 72

Docosahexaenoic acid (DHA) is essential for the growth and functional development of the brain in infants. DHA is also required for maintenance of normal brain function in adults. The inclusion of plentiful DHA in the diet improves learning ability, whereas deficiencies of DHA are associated with deficits in learning. DHA is taken up by the brain in preference to other fatty acids. The turnover of DHA in the brain is very fast, more so than is generally realized. The visual acuity of healthy, full-term, formula-fed infants is increased when their formula includes DHA. During the last 50 years, many infants have been fed formula diets lacking DHA and other omega-3 fatty acids. DHA deficiencies are associated with foetal alcohol syndrome, attention deficit hyperactivity disorder, cystic fibrosis, phenylketonuria, unipolar depression, aggressive hostility, and adrenoleukodystrophy. Decreases in DHA in the brain are associated with cognitive decline during aging and with onset of sporadic Alzheimer disease. The leading cause of death in western nations is cardiovascular disease. Epidemiological studies have shown a strong correlation between fish consumption and reduction in sudden death from myocardial infarction. The reduction is approximately 50% with 200 mg day(-1)of DHA from fish. DHA is the active component in fish. Not only does fish oil reduce triglycerides in the blood and decrease thrombosis, but it also prevents cardiac arrhythmias. The association of DHA deficiency with depression is the reason for the robust positive correlation between depression and myocardial infarction. Patients with cardiovascular disease or Type II diabetes are often advised to adopt a low-fat diet with a high proportion of carbohydrate. A study with women shows that this type of diet increases plasma triglycerides and the severity of Type II diabetes and coronary heart disease. DHA is present in fatty fish (salmon, tuna, mackerel) and mother's milk. DHA is present at low levels in meat and eggs, but is not usually present in infant formulas. EPA, another long-chain n-3 fatty acid, is also present in fatty fish. The shorter chain n-3 fatty acid, alpha-linolenic acid, is not converted very well to DHA in man. These longchain n-3 fatty acids (also known as omega-3 fatty acids) are now becoming available in some foods, especially infant formula and eggs in Europe and Japan. Fish oil decreases the proliferation of tumour cells, whereas arachidonic acid, a longchain n-6 fatty acid, increases their proliferation. These opposite effects are also seen with inflammation, particularly with rheumatoid arthritis, and with asthma. DHA has a positive effect on diseases such as hypertension, arthritis, atherosclerosis, depression, adult-onset diabetes mellitus, myocardial infarction, thrombosis, and some cancers.
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PMID:Health benefits of docosahexaenoic acid (DHA) 1047 62

There has been an increasing number of patients with dementia in Japan. Although such patients were hospitalized longer than in other countries, the length of the hospital stay is becoming shorter due to changes in insurance systems. Therefore, the families of such patients are experiencing greater stress. In order to investigate the efficacy of a group structured intervention, 20 family caregivers participated in a series of five weekly sessions, each of which consisted of an educational approach, problem-solving techniques, psychological support, and relaxation. All family caregivers were women whose ages ranged from 47-66 years (mean= 54.7 +/- 4.4). The period of care at home ranged from 1-12 years (mean= 5.8 +/- 2.7). Concerning the original disease of patients, 10 had vascular dementia and 8 had senile dementia of Alzheimer type (Alzheimer disease). Two psychometries, i. e., Profile of Mood States (POMS) and General Health Questionnaire-30 (GHQ-30), were administered pre- and post-intervention. The results indicated that there was significant improvement (p<0.05) in the scores of depression, anger-hostility, fatigue, confusion in the POMS, and physical symptoms, anxiety-mood disorder, and suicidality-depression in the GHQ-30. This preliminary study suggests that this kind of intervention appears quite effective for relieving the emotional and physical discomfort suffered by family caregivers.
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PMID:A structured intervention for family caregivers of dementia patients: a pilot study. 1053 Jun 24

The effects of peptide fragments of the beta-amyloid precursor protein (betaAPP) on parallel fiber (PF)-Purkinje cell synaptic transmission in the rat cerebellum were examined. Transient inward currents associated with calcium influx were induced by localized applications of the 105-amino acid carboxy-terminal fragment (CT105) of betaAPP to discrete dendritic regions of intact Purkinje cells. betaAPP and the amyloid beta (Abeta) peptide fragments Abeta1-16, Abeta25-35, and Abeta1-42 had little or no effect. Inward currents were also observed following applications of CT105 to isolated patches of somatic Purkinje cell membrane. All five proteins/peptides induced some depression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor-mediated synaptic transmission between PFs and Purkinje cells, through a combination of pre- and postsynaptic effects. CT105 induced the greatest depression, which spread to distant synapses following local application and which was prevented by inhibition of nitric oxide synthase. These data indicate that CT fragments of the betaAPP can modulate AMPA-mediated glutamatergic synaptic transmission in the cerebellar cortex. These fragments may therefore be considered alternative candidates for some of the neurotoxic effects of Alzheimer's disease.
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PMID:Peptide fragments of beta-amyloid precursor protein: effects on parallel fiber-Purkinje cell synaptic transmission in rat cerebellum. 1069 43

Multiple studies of individuals with Alzheimer disease have substantiated significant levels of informant-rated change in several domains and facets of the Neuroticism-Extraversion-Openness Personality Inventory, including increases in Neuroticism and decreases in Extraversion and Conscientiousness relative to premorbid personality traits. Decline in Openness was cited in some reports, and replicable changes were identified in several facets. Current and premorbid personality of 50 patients with Alzheimer disease were rated by informants using the Neuroticism-Extraversion-Openness Personality Inventory. Multiple regression analysis was used to assess possible relationships of levels of reported change with covariates, including premorbid rating, education, duration of dementia, age, gender, and Mini-Mental State Examination score. Premorbid rating was the only significant predictor of reported change for Neuroticism, Extraversion, Conscientiousness, and the facets Anxiety (N1), Assertiveness (E3), and Activity (E4). Rated change in Depression was also found to be related to duration of dementia, change in Vulnerability was influenced by gender, and reported change in both Openness and Ideas showed a relationship to level of education.
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PMID:Premorbid personality predicts level of rated personality change in patients with Alzheimer disease. 1071

Agitation and aggressiveness are frequent in the elderly and often related to dementia. As a result of the ageing of the general population this is becoming a major public health concern. No or little epidemiological data, during primary health care, about symptoms, co-morbidity, nor medical and social consequences of elderlys' disruptive behavior have been gathered or published in the French literature. Thus, in order to describe these disorders, a survey in cooperation with general practitioners (GP) was conducted. A representative sample of 212 French GP's, all with preferential geriatric activity were asked to conduct a study by including retrospectively their two most recent patients older than 65, who had exhibited agitation and/or aggressiveness. From this cross sectional study, 410 patients (female: 61%, male: 39%) were included. The mean age was 81 years (sd: 7.65). The patients suffered from change in verbal behavior (80%), verbal aggressiveness (71%), physical agitation (60%), wandering (48%), and/or physical aggressiveness (31%). The average of disruptive behavior symptoms per patient was 2.9. The symptoms appeared progressively in 81% of patients, the mean duration was two years and it was the first episode in 40% of patients. Disruptive behaviors may be explained in view of organic illness in 62% of patients (cardiovascular disease: 37%, neurologic: 12%, diabetes: 7%, dehydratation: 5%), dementia (Alzheimer disease: 20%, vascular dementia: 18%, mixed dementia: 14%). In 54% of patients disruptive behavior may be explained in view of depression: 34%, and anxiety disorder: 31%. A triggering factor was observed in 57% of cases (psychosocial stress: 39%). Somatic consequences of the symptoms were frequently identified: decrease of alimentary intake: 39%, weight loss: 27%, dehydratation: 11%, falls: 32%, and irregular medication intake: 31%. Limitation of daily life activities: 85%, and family life: 97% were also noted. Acceptability of patient's symptoms by the family was good (no discomfort or transitory and mild irritability) in 61% of cases, and very bad (reactions of exhaustion, hospitalization requirement) in 13%. This study carried out during primary care, showed that the elderly's disruptive behaviors cause severe medical consequences and familial and social distress.
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PMID:[Causes and consequences of elderly's agitated and aggressive behavior]. 1087 60

Event related potentials have been examined in depression and Alzheimer disease like clinical utility. To evaluate the influence of visual and auditory stimuli on the P300 latency we studied 12 patients with major depression, 12 patients with Alzheimer disease and 12 normal subjects. The experimental tasks applied was, first a series of 300 auditory stimuli, 255 (85%), with tones of 1,000 Hz, and considered as the frequent stimulus, whereas 45 (15%) were tones of 2,000 Hz and referred as the rare stimulus. A second series of 300 visual stimuli, 255 (85%) that were black circles on a white background, and considered the frequent stimulus (9 cm diameter, 200 ms duration), whereas 45 (15%) were black squares on a white background and referred as the rare stimulus (9 cm diameter, 200 ms duration) in the centre of a computer screen. The results show an increase of P300 latency in depressive and Alzheimer patients during auditory and visual tasks. Differences were found in reaction time to visual or auditory stimuli in Alzheimer disease. These results are consistent with an impairment in brain function in depressive patients that is associated with cortical hypoactivity and deficits in perceptive, auditory or visual, functions, whereas deterioration in Alzheimer's disease is sensorymotor, according to the slowness latency in the reaction time.
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PMID:Deficit in sensory motor processing in depression and Alzheimer's disease: a study with EMG and event related potentials. 1103 20

Alzheimer's disease is the most common cause of memory disruption in elderly people. The main pathogenic factor of the disease is beta-amyloid protein, which may cause toxic damage of neurones. Other suggested pathogenic factors include an inflammatory process around the senile plaques, apoptosis and necrotic death of neurones, and, in consequence, changes in functioning of neurotransmitter systems. In this article the authors present the main directions in pharmacotherapy of Alzheimer's disease: causal therapy, which prevents the neurodegenerative changes and slows down the pathogenetic process, and symptomatic therapy. The aim of symptomatic therapy is to reduce memory disruption and psychiatric symptoms associated with the disease. Positive influence on cognitive processes is exerted by cholinergic drugs, e.g. the actually used inhibitors of acetylcholinesterase (rivastigmine, donepezil), the nootropic agents (piracetam, nefiracetam) and extracts of Gingko biloba. For treatment of the disease accompanying psychiatric symptoms (anxiety, depression, hallucinations, sleepness) the drugs with minimal influence on cognitive processes are recommended. Attempts at causal therapy are focussed on searching for the substances that can prevent the formation and toxicity of beta-amyloid (droloksifen, estrogens, agonists of muscarinic receptors M1), the cytotoxic influence of excitatory aminoacids (memantine, lamotrigine), calcium (nimodipine) and free radicals (selegiline, alpha-tocoferol), and the development of inflammatory process (non-steroidal antiinflammatory drugs). The new target of research is correction of deficits of nerve growth factor and neurotransmitters by intracerebral implantation of modified fibroblasts. Another way is prevention of the formation of amyloid plaques using appropriate antisense oligonucleotides.
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PMID:[Perspectives of therapy of Alzheimer's disease]. 1105 61


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