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J I Lao

Publications and source records attributed to J I Lao.

8 recordsLinked to original sources
PubMed2001

Alzheimer's disease and the cystatin C gene polymorphism: an association study.

Cystatin C is an amyloidogenic protein that colocalizes with beta-amyloid (Abeta) within arteriolar walls in Alzheimer disease (AD) brains. Recently, a coding polymorphism in the cystatin C gene (CST3) has been claimed to confer risk for the development of late-onset AD. In the present work we have tested the frequencies of CST3-A and CST3-G alleles and used chi-square and logistic regression analyses to assess the association among the CST3 polymorphism, apolipoprotein E4 (APOE4), and AD in a series of 159 AD patients and 155 controls. The CST3-A allele was seen to be an accumulation risk factor for early-onset AD. Furthermore, a synergistic association among the CST3-A allele, APOE4 and AD was found in AD patients whose ages were between 60 and 74 years.

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PubMed1998

A novel mutation in the predicted TM2 domain of the presenilin 2 gene in a Spanish patient with late-onset Alzheimer's disease.

Mutations in the presenilin-2 (PS-2) gene are less frequent than mutations in the PS-1 gene. All mutations described in the PS-1 gene were found in early-onset Alzheimer's disease (AD) patients. At present, there are two missense mutations described for the PS-2 gene in some AD pedigrees. We have therefore analyzed transmembrane 2 (TM2) and TM5 domains of the PS-2 gene in AD patients and in a group of age-matched healthy controls. In a patient who was clinically diagnosed as having late-onset AD, we found a novel missense mutation consisting of a G->A substitution on exon 5 of the PS-2 gene, which results in a Val to Ile substitution at codon 148 within the predicted TM2 domain of the PS-2 protein. This is the third mutation described in the PS-2 gene and the first presenilin mutation detected in a Spanish AD patient. Both, the N141I mutation and the V148I mutation described here are located within the predicted TM2 domain and both were found in late-onset AD kindreds, whereas the mutation within the predicted TM5 domain was found in an early-onset AD pedigree. Carriers of mutations within TM2 of PS-1 have a mean age at onset of 40 years, while the other mutations in PS-1 occur in families with a mean age at onset of 47 years. In summary, we report here the first mutation in a presenilin gene in a Spanish AD case, which is the third mutation detected for the PS-2 gene.

Adult↗
PubMed1997

A general method for DNA polymorphism identification in genetic assessment and molecular diagnosis.

A general methodology for the analysis of human diseases at the nucleic acid level has been described. This method consists of a semiautomated, nontoxic analytic procedure, staining DNA bands with silver nitrate instead of ethidium bromide after DNA amplification by PCR. This technique provides a sensitive assay with enhanced accuracy and offers the possibility of carrying out the molecular analysis of several polymorphisms in a single day simplifying molecular genetics with diagnostic purposes.

DNA↗
PubMed1997

Behavioral changes associated with different apolipoprotein E genotypes in dementia.

Behavioral dysfunction is a problem in patients with Alzheimer disease (AD), and is apparent in up to 67% of individuals. Such changes are a primary cause of individual institutionalization and often lead to their functional disability. As AD progresses, the worsening of behavioral dysfunction becomes increasingly evident and is linked with decreased patient survival. Unfortunately, some of the more common drug therapies used in AD patients to stabilize other facets of their disease worsen behavioral dysfunction. Behavioral changes are associated with endogenous and exogenous factors such as disease stage, environmental factors, other medical conditions, drug regimen, and AD genotype. The most commonly examined and important genotype in AD is the apolipoprotein E (APO E) series, and APO E genotyping is also a useful diagnostic tool. The most frequent APO E genotypes encountered in AD are APO E-4/4, APO E-3/4, and APO E-3/3. In the current study, AD behavioral dysfunction, anxiety, and psychoses were commonly associated with the APO E-3/3 genotype, whereas disorientation, agitation, depression and motor disorders were common among patients with the APO E-4/4 and APO E-3/4 genotypes. These differences were not statistically significant but they suggest that different APO E genotypes influence the phenotypic expression of specific noncognitive symptoms, including behavioral function, in AD.

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PubMed1996

APOE-related frequency of cognitive and noncognitive symptoms in dementia.

Although memory disorders and the aphaso-apraxo-agnosic syndrome are the most relevant clinical symptoms in dementia, behavioral changes, mood-related disturbances and sleep disorders are the major cause of institutionalization and caregiver concern. In the present study we have investigated the frequency and progression of cognitive and noncognitive symptoms in Alzheimer's disease (AD) as well as the APOE-related frequency of clinical symptoms in dementia. Memory decline (100%), aphasia (94%), apraxia (99%), agnosia (94%) and motor dysfunction (90%) appeared in practically all cases with mild (GDS-3), moderate (GDS 3-4) and severe (GDS 6-7) dementia. The most frequent noncognitive symptoms include anxiety (76%), depression (68%), behavioral changes (67%), psychotic symptoms (43%), sleep disorders (43%), incontinence (23%) and cerebrovascular symptoms (75%). Anxiety, depression, behavioral changes, psychotic symptoms, motor dysfunction and cognitive deterioration paralleled the severity of dementia, increasing their frequency from mild to severe dementia. The most important sleep disorders were irregular sleep-wake pattern (67%) and insomnia (47%). Disorientation (90%) and drug administration (88%) appeared to be the most important factors in causing sleep disorders in dementia. Disorientation, agitation and motor disorders were slightly more frequent in patients with APOE-4/4, while anxiety and sleep disorders appeared more frequently in APOE-3/4. Behavioral changes and psychotic symptoms did not show any clear association with specific APOE subtypes. In conclusion, our results suggest that noncognitive symptoms are very important clinical events in the disease progression and in decision making for therapeutic intervention and institutionalization. Furthermore, it is likely that some brain dysfunctions leading to particular clinical symptoms might be associated with specific AD genotypes.

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