OBJECTIVES: Seoul-Activities of Daily Living(S-ADL) was developed to assess elderly person's basic activities of daily living. This study aims to develop standardized ADL assessment scale and confirm the reliability and validity of the S-ADL. METHODS: It was participated in 336 controls and 145 patients diagnosed Alzheimer's disease. RESULTS: In controls, it was statistically significant to age, but not sex, education, region and presence of spouse. Also, reliability and validity were statistically significant. Principal axis factoring analysis revealed three factors that accounted for 66.67% of the total variance(1.self-care/hygiene, 2.ambulation, 3.toileting). According to each CDR stage, there were significant difference, except for CDR 0.5 and CDR 1 suggesting early dementia. Particularly, it was remarkable for functional impairment in CDR 2 and CDR 3 suggesting moderate to severe dementia. The order of the loss of function was (1) self-care/hygiene, (2) toileting, and (3) ambulation. CONCLUSIONS: Our study showed that the S-ADL could be a very reliable and valid tool for the assessment of functional disabilities of Korean dementia patients. Particularly, S-ADL would be useful in assessing daily function of moderate to severe AD.
Activities of Daily Living ; Aged ; Alzheimer Disease ; Axis, Cervical Vertebra ; Dementia ; Education ; Humans ; Reproducibility of Results* ; Spouses ; Walking

Previous studies have shown disrupted synaptic plasticity and neural activity in depression. Such alteration is strongly associated with disrupted synaptic structures. Chronic stress has been known to induce changes in dendritic structure in the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC), but antidepressant effect on structure of these brain areas has been unclear. Here, the effects of imipramine on dendritic spine density and morphology in BLA and mPFC subregions of stressed mice were examined. Chronic restraint stress caused depressive-like behaviors such as enhanced social avoidance and despair level coincident with differential changes in dendritic spine structure. Chronic stress enhanced dendritic spine density in the lateral nucleus of BLA with no significant change in the basal nucleus of BLA, and altered the proportion of stubby or mushroom spines in both subregions. Conversely, in the apical and basal mPFC, chronic stress caused a significant reduction in spine density. The proportion of stubby or mushroom spines in these subregions overall reduced while the proportion of thin spines increased after repeated stress. Interestingly, most of these structural alterations by chronic stress were reversed by imipramine. In addition, structural changes caused by stress and blocking the changes by imipramine were corelated well with altered activation and expression of synaptic plasticity-promoting molecules such as phospho-CREB, phospho-CAMKII, and PSD-95. Collectively, our data suggest that imipramine modulates stress-induced changes in synaptic structure and synaptic plasticity-promoting molecules in a coordinated manner although structural and molecular alterations induced by stress are distinct in the BLA and mPFC.

T-vectors are widely used for cloning the polymerase chain reaction (PCR) products. However, the low conversion efficiency of a plasmid into the linear T-vector usually results in non-recombinants. Here, we designed a new plasmid pNBQ-T to easily select the recombinant colonies harboring PCR products. pNBQ-T plasmid, which contains a DsRed indicator gene between two Nt.BspQI restriction cassettes, each of which contains palindromic sequences susceptible to Nt.BspQI nickase (5′-GCTCTTCT^GAAGAGC-3′) at each end. Thus, this plasmid can be easily converted into T-vectors by a nickase (quadruple nicking), which results in two double strand breaks with 3′-thymidine overhangs. DsRed indicator gene, which is inserted between the restriction sites, helps identifying the PCR recombinants. Using this pNBQ-T plasmid the insertion efficiency of a PCR product was examined. We successfully identified white colony of the recombinants with the inserted myostatin promoter gene: the cloning efficiency was 93%. Therefore, this simple method utilizing pNBQ-T plasmid will serve as a useful and efficient technique for preparation of home-made T-vectors.
Clone Cells ; Cloning, Organism ; Deoxyribonuclease I* ; Methods ; Myostatin ; Plasmids ; Polymerase Chain Reaction

OBJECTIVES: There are evidences of apoptotic neuronal cell death in Alzheimer's disease (AD). Recent studies suggested AD pathogenesis in the central nervous system as well as in peripheral lymphocytes. The object of this study is to compare the cell viability and the proliferation activity in AD patients with healthy normal control by using peripheral lymphocytes. METHODS: We analyzed the cell viability and the proliferation activity of phytohemagglutinin (PHA)-activated lymphocytes from 73 AD patients and 31 normal contols. The cell viability and the proliferation activity were measured at baseline (T0), 24 hours (T24), 48 hours (T48), 72 hours (T72), 96 hours (T96), by the tryphan blue method and the BrdU proliferation activity method, respectively. RESULTS: The cell viability of PHA-activated peripheral lymphocytes in AD patients was significantly decreased at T72, T96 compared with healthy controls (F=8.034, p<0.001). In AD patients, the decline of proliferation activity appeared in earlier than healthy normal controls. CONCLUSION: This study suggests that there is a decreased cell viability and the proliferation activity of peripheral lymphocytes in AD patients. These finding may be related with the increased apoptosis in Alzheimer's disease.
Alzheimer Disease* ; Apoptosis ; Bromodeoxyuridine ; Cell Death ; Cell Survival* ; Central Nervous System ; Humans ; Lymphocytes* ; Neurons

The polymorphism at codon 129 (M129V) of the human prion protein gene (PRNP) is a known risk factor for Creutzfeldt-Jakob disease (CJD) in Caucasians. There are few reports of this polymorphism's effect on memory and on the risk of Alzheimer's disease (AD). The M129V genotype distributions among Asians are very different from Caucasians. Another polymorphism, codon 219 (E219K) is not found in Caucasians. We investigated two polymorphisms of PRNP, M129V (rs1799990) and E219K (rs1800014) in 297 Korean AD patients and 217 healthy subjects. The analysis of the genotype and allele distributions showed no significant difference between the AD patients and the controls in both polymorphisms (P=0.19 genotype, P=0.51 allele for M129V; P=0.64 genotype, P=0.50 allele for E219K). Also, the PRNP polymorphisms were not significantly associated with AD when the populations were stratified for the presence or absence of apolipoprotein E-e4 (ApoE-epsilon4) allele. These results suggest that the PRNP genetic variants are not associated with the risk for AD in Korean population.
Prions/*genetics ; Polymorphism, Genetic/*genetics ; Male ; Korea/epidemiology ; Humans ; Genotype ; Genetic Predisposition to Disease/genetics ; Female ; Codon/genetics ; Apolipoproteins E/genetics ; Alzheimer Disease/*epidemiology/*genetics ; Alleles ; Aged

Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α-induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α.Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

Myristoylated alanine-rich C kinase substrate (MARCKS) is a widely distributed protein kinase C (PKC) substrate and has been implicated in actin cytoskeletal rearrangement in response to extracellular stimuli. Although MARCKS was extensively examined in various cell culture systems, the physiological function of MARCKS in the central nervous system has not been clearly understood. We investigated alterations of cellular distribution and phosphorylation of MARCKS in the hippocampus following kainic acid (KA)-induced seizures. KA (25 mg/kg, i.p.) was administered to eight to nine week-old C57BL/6 mice. Behavioral seizure activity was observed for 2 h after the onset of seizures and was terminated with diazepam (8 mg/kg, i.p.). The animals were sacrificed and analyzed at various points in time after the initiation of seizure activity. Using double-labeling immunofluorescence analysis, we demonstrated that the expression and phosphorylation of MARCKS was dramatically upregulated specifically in microglial cells after KA-induced seizures, but not in other types of glial cells. PKC alpha, beta I, beta II and delta, from various PKC isoforms examined, also were markedly upregulated, specifically in microglial cells. Moreover, immunoreactivities of phosphorylated MARCKS were co-localized in the activated microglia with those of the above isoforms of PKC. Taken together, our in vivo data suggest that MARCKS is closely linked to microglial activation processes, which are important in pathological conditions, such as neuroinflammation and neurodegeneration.
Up-Regulation/drug effects ; Time Factors ; Seizures/chemically induced/*metabolism ; Protein Kinase C-delta/analysis ; Protein Kinase C-alpha/analysis ; Protein Kinase C/*analysis ; Protein Biosynthesis/drug effects ; Phosphorylation/drug effects ; Microscopy, Confocal ; Microglia/cytology/drug effects/*metabolism ; Mice, Inbred C57BL ; Mice ; Membrane Proteins/*analysis/metabolism ; Kainic Acid/*toxicity ; Isoenzymes/analysis ; Intracellular Signaling Peptides and Proteins/*analysis/metabolism ; Immunohistochemistry ; Animals

OBJECTIVES: Seoul-Instrumental Activities of Daily Living (S-IADL) was developed to assess elderly person's instrumental everyday activities. This study aims to develop standardized IADL assessment scale and to confirm the reliability and validity of the S-IADL. METHODS: The 336 controls were included in standardization study. Reliability and validity of S-IADL were tested by 72 Alzheimer's disease patients and 72 controls matched to age, sex, and education. We also conducted Receiver Operating Characteristics curve for sensitivity and specificity of S-IADL. RESULTS: Because of positively skewed distribution of S-IADL, standardization data were presented using 1SD and 2SD value. Internal consistency, test-retest reliability, and interrater reliability were statistically significant. Principal axis factoring analysis revealed two factors that accounted for 59.95% of the total variance, and second factor was items sensitive to sex (3.preparing food/cooking, 4.household chores). S-IADL was correlated significantly with other standardized cognitive measures, demonstrating good convergent validity. With a cut-off point of 8, the S-IADL had a sensitivity of 83.3% and specificity of 93.1% in the diagnosis of dementia. Also, with a 2SD standardized data, sensitivity was 81.9% and specificity was 93.1%. CONCLUSION: Our study showed that the S-IADL could be a reliable and valid tool for the assessment of functional disabilities of Korean dementia patients. Particularly, S-IADL had higher sensitivity and specificity than other IADL instruments, suggesting that it is useful to early detection of dementia.
Activities of Daily Living ; Aged ; Alzheimer Disease ; Axis, Cervical Vertebra ; Dementia ; Diagnosis ; Education ; Humans ; Reproducibility of Results* ; ROC Curve ; Sensitivity and Specificity

OBJECTIVE: We evaluated cell viability and proliferation activity of peripheral lymphocytes as potential models of neuronal death in Alzheimer's disease (AD). METHODS: We analyzed the cell viability and proliferation activity of phytohemagglutinin (PHA)-activated lymphocytes from 68 AD patients and 33 normal controls. The cellular measures were made at baseline (0 hr), 24 hrs, 48 hrs, 72 hrs, and 96 hrs after PHA stimulation. RESULTS: Cell viability in the AD patients was significantly decreased at 72 hrs and 96 hrs, compared with the normal controls. The declining ramp of the proliferation activity from 48 hrs to 72 hrs after PHA stimulation was significantly related to cell viability at 72 hrs and at 96 hrs in the AD patients. CONCLUSION: Lymphocytes from patients with AD have altered viability and proliferation characteristics in culture following PHA stimulation. These findings suggest that lymphocytes may be used as a peripheral tissue model of cell cycle dysregulation in AD.
Alzheimer Disease ; Architectural Accessibility ; Cell Cycle ; Cell Death ; Cell Survival ; Humans ; Lymphocytes ; Neurons

OBJECTIVE: Biological markers for Alzheimer's disease (AD) will help clinicians make objective diagnoses early during the course of dementia. Previous studies have suggested that cell cycle dysregulation begins earlier than the onset of clinical manifestations in AD. METHODS: We examined the lymphocyte expression of cell cycle proteins in AD patients, dementia controls (DC), and normal controls (NC). One-hundred seventeen subjects (36 AD, 31 DC, and 50 NC) were recruited. The cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were measured in peripheral lymphocytes. Cell cycle protein expression in the three groups was compared after adjusting for age and sex. RESULTS: The levels of cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were significantly higher in AD patients than in the NC subjects. The DC group manifested intermediate levels of cell cycle proteins compared with the AD patients and the NC subjects. The present study indicates that cell cycle proteins are upregulated in the peripheral lymphocytes of AD patients. CONCLUSION: Cell cycle dysregulation in peripheral lymphocytes may present a promising starting point for identifying peripheral biomarkers of AD.
Alzheimer Disease* ; Biomarkers ; Cell Cycle Proteins* ; Cell Cycle* ; Cyclin B ; Cyclin D ; Cyclins ; Dementia ; Diagnosis ; Humans ; Lymphocytes*