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Judith Harris

Publications and source records attributed to Judith Harris.

6 recordsLinked to original sources
PubMed2006

Role of 5HT 2A and 5HT 2C polymorphisms in behavioural and psychological symptoms of Alzheimer's disease.

OBJECTIVE: Alzheimer's disease (AD) patients suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. Polymorphisms within serotonin receptors 5HT(2A) and 5HT(2C) have been previously investigated in a few interesting studies reviewed here, however, their role remains unclear. METHODS: Our large cohort of 394 patients had longitudinal information on the BPSD (Neuropsychiatric Inventory), which was used to dichotomise patients into whether they had ever suffered from a given symptom within the study period and give each patient a severity score. These measures were related to the 5HT(2A) T102C and 5HT(2C) cys23ser genotype and allele frequencies. RESULTS: Our data supports previous reports of an increased frequency of the C allele and CC genotype of the T102C variant of 5HT(2A) with hallucinations, delusions, psychosis and aberrant motor behaviour, however, we dispute previous associations with depression and aggression. We describe for the first time an increase in the C allele and CC genotype frequencies of the cys23ser variant of 5HT(2C) with anxiety and support previous associations with appetite disturbances in females. CONCLUSION: This review and extension of previous data presents support for the role of 5HT(2A) and 5HT(2C) in the development of certain symptoms, although the effect size may be small.

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PubMed2005

Association study and meta-analysis of low-density lipoprotein receptor related protein in Alzheimer's disease.

Genome scans in sporadic Alzheimer's disease (AD) have revealed a possible susceptibility locus on chromosome 12. The low density lipoprotein receptor related protein (LRP1) gene lies within this area of linkage. Eighteen previous AD case-control studies have investigated the C766T polymorphism in LRP1 with conflicting results, including a protective effect on AD of the T allele, an increased susceptibility towards AD with both the C and T alleles, or no association at all. We have now performed a case-control study based on a large UK cohort of 477 AD patients and 466 matched controls, and have included these data, with those drawn from the 18 previous studies, into in a meta-analysis of 4668 AD patients and 4473 controls. We find no evidence for influence on the risk for AD in either our own present cohort or in the combined data set. Furthermore, we investigated whether the C766T polymorphism might modify the clinical and pathological phenotype in our cohort. We found no association with AD when the cohort was stratified into those with early (<65 years) or late (>65 years) onset, or when split into Apolipoprotein E (APOE) epsilon4 bearers and epsilon4 non-bearers. In addition, the C766T polymorphism was shown not to influence the age onset of AD. In a separate autopsy-confirmed cohort of 130 AD cases, no association with genotype or allele was observed for tissue levels of beta-amyloid 40, beta-amyloid 42, total beta-amyloid, pathological tau proteins, microglial cells or extent of astrocytic activity. Therefore, in this present study, we find no evidence for the involvement of this polymorphism either in increasing the susceptibility to AD, or by acting as a phenotypic modifier.

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PubMed2004

Interleukin-6 promoter polymorphism: risk and pathology of Alzheimer's disease.

Inflammatory and immune responses are involved in the pathogenesis of Alzheimer's disease (AD). Interleukin-6 (IL-6), an inflammatory cytokine, is thought to play a role in neurodegeneration of the central nervous system and has been associated with increased amyloid precursor protein expression in vitro and greater cognitive decline. Previously a C-174G polymorphism in the promoter of IL-6, which influences expression in vitro, has been found associated in some studies but not all. We investigated this polymorphism in a large independent UK sample of AD cases (n = 356) and controls (n 434) but found no association. We extended the study to genotype/phenotype correlations but found no correlation with age of onset (n = 338), brain amyloid load (n = 126) or Tau load (n = 101), brain microglial cell load (n = 65) or brain reactive astrocytes (n = 127). Our data do not support a pathogenic role in AD for the C-174G polymorphism in isolation.

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PubMedDate not supplied

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