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Biomedical subjects

S Lovestone

Publications and source records attributed to S Lovestone.

At least 91 records · Page 5Linked to original sources
PubMed1996

Apolipoprotein E: non-cognitive symptoms and cognitive decline in late onset Alzheimer's disease.

OBJECTIVES: To determine the association between the epsilon2 and epsilon4 alleles of apolipoprotein E (ApoE) and independent measures of cognitive decline and non-cognitive symptomatology in late onset Alzheimer's disease. METHODS: The frequency of the epsilon2 and epsilon4 alleles of ApoE and their association with measures of cognitive decline and non-cognitive symptomatology were assessed in a population based case register study of 164 patients with late onset Alzheimer's disease from the east Lambeth and south Southwark districts of south London. RESULTS: Analysis of a wide range of non-cognitive symptoms against ApoE epsilon4 genotype showed no significant association but a positive relation was found between ApoE epsilon2 genotype and depressive symptomatology (P = 0.004). No relation was found between measurements of cognitive decline and the presence of the ApoE epsilon4 allele. A trend for decreasing age at onset of 3 to 4 years in carriers of the ApoE epsilon4 allele was found, confirming earlier studies. CONCLUSION: Presence of the epsilon4 allele of ApoE is associated with an earlier age at onset but does not seem to be related to either a more severe psychopathology or a more rapid progression of the illness. The epsilon2 allele of ApoE is associated with depressive symptomatology in late onset Alzheimer's disease.

Age of Onset↗
PubMed1996

Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop.

Recent neuropathologic autopsy studies found that 15 to 25% of elderly demented patients have Lewy bodies (LB) in their brainstem and cortex, and in hospital series this may constitute the most common pathologic subgroup after pure Alzheimer's disease (AD). The Consortium on Dementia with Lewy bodies met to establish consensus guidelines for the clinical diagnosis of dementia with Lewy bodies (DLB) and to establish a common framework for the assessment and characterization of pathologic lesions at autopsy. The importance of accurate antemortem diagnosis of DLB includes a characteristic and often rapidly progressive clinical syndrome, a need for particular caution with neuroleptic medication, and the possibility that DLB patients may be particularly responsive to cholinesterase inhibitors. We identified progressive disabling mental impairment progressing to dementia as the central feature of DLB. Attentional impairments and disproportionate problem solving and visuospatial difficulties are often early and prominent. Fluctuation in cognitive function, persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are core features with diagnostic significance in discriminating DLB from AD and other dementias. Appropriate clinical methods for eliciting these key symptoms are described. Brainstem or cortical LB are the only features considered essential for a pathologic diagnosis of DLB, although Lewy-related neurites, Alzheimer pathology, and spongiform change may also be seen. We identified optimal staining methods for each of these and devised a protocol for the evaluation of cortical LB frequency based on a brain sampling procedure consistent with CERAD. This allows cases to be classified into brainstem predominant, limbic (transitional), and neocortical subtypes, using a simple scoring system based on the relative distribution of semiquantitative LB counts. Alzheimer pathology is also frequently present in DLB, usually as diffuse or neuritic plaques, neocortical neurofibrillary tangles being much less common. The precise nosological relationship between DLB and AD remains uncertain, as does that between DLB and patients with Parkinson's disease who subsequently develop neuropsychiatric features. Finally, we recommend procedures for the selective sampling and storage of frozen tissue for a variety of neurochemical assays, which together with developments in molecular genetics, should assist future refinements of diagnosis and classification.

Dementia↗
PubMed1995

Stimulation of MAP kinase by v-raf transformation of fibroblasts fails to induce hyperphosphorylation of transfected tau.

A proportion of the microtubule-associated protein, tau, is in an elevated state of phosphorylation in foetal and adult brain whereas all of the tau in paired helical filaments, which are characteristic of Alzheimer's disease is hyperphosphorylated; it is important therefore to elucidate the mechanisms that regulate tau phosphorylation. Here we describe results that show that although MAP kinase can hyperphosphorylate tau in vitro, activation of MAP kinase in transformed fibroblasts does not result in hyperphosphorylation of transfected tau, whereas glycogen synthase kinase-3 beta (GSK-3 beta) when co-transfected with tau does result in tau hyperphosphorylation. The findings imply that GSK-3 beta may be a stronger candidate than MAP kinase for inducing tau hyperphosphorylation in vivo.

3T3 Cells↗
PubMed1995

The role of the father in parental postnatal mental health.

Contrary to idealized images of parenthood, the months immediately following childbirth are characterized by enhanced rates of parental mental illness and filicide. In this paper we consider fathers and their role in the postnatal well-being of the parturient couple. The process of becoming a father is influenced by not only the man's internal and external experiences of 'father', but also the woman's, since the new infant's relationship with father is mediated by mother and her conjugal relationship with father. When a couple's prenatal relationship is based on a system of shared parental constructs involving a denigrated father and overvalued mother and a concomitant intolerance of the idea of a creative (Oedipal) couple, they will experience particular difficulties in adjusting to the new family configuration. In working with individuals or couples who have experienced post-partum psychological difficulties it is important to remember that not only maternal imagos but also paternal and conjugal ones need to be addressed.

Adult↗
PubMed1995

Abnormally phosphorylated tau protein in senile dementia of Lewy body type and Alzheimer disease: evidence that the disorders are distinct.

The relationship between Alzheimer disease (AD) and dementia with Lewy bodies (senile dementia Lewy body type, or SDLT) and dementia in Parkinson's disease is unclear. AD pathology is characterised by both amyloid deposition and abnormal phosphorylation of tau in paired helical filaments (PHF-tau). In AD, abnormally phosphorylated PHF-tau is present in neurofibrillary tangles, in neuritic processes of senile plaques, and also in neuropil threads dispersed throughout the cerebral cortex. Cortical homogenates from 12 cases each of AD and SDLT, 13 cases of Parkinson's disease, and 11 normal controls were examined by Western blot analysis with antibodies that detect PHF-tau. No PHF-tau was found in Parkinson's disease or control cortex. No PHF-tau was found in SDLT cases without histological evidence of tangles. PHF-tau was detectable in SDLT cases with a low density of tangles, and large amounts of PHF-tau were present in AD cases. This study demonstrates that abnormally phosphorylated PHF-tau is only present where tangles are found and not in SDLT cases without tangles or with only occasional tangles. It is concluded that Lewy body dementias are distinct at a molecular level from AD.

Aged↗
PubMed1994

Alzheimer's disease-like phosphorylation of the microtubule-associated protein tau by glycogen synthase kinase-3 in transfected mammalian cells.

BACKGROUND: Paired helical filaments (PHFs) are a characteristic pathological feature of Alzheimer's disease; their principal component is the microtubule-associated protein tau. The tau in PHFs (PHF-tau) is hyperphosphorylated, but the cellular mechanisms responsible for this hyperphosphorylation have yet to be elucidated. A number of kinases, including mitogen-activated protein (MAP) kinase, glycogen synthase kinase (GSK)-3 alpha, GSK-3 beta and cyclin-dependent kinase-5, phosphorylate recombinant tau in vitro so that it resembles PHF-tau as judged by its reactivity with a panel of antibodies capable of discriminating between normal tau and PHF-tau, and by a reduced electrophoretic mobility that is characteristic of PHF-tau. To determine whether MAP kinase, GSK-3 alpha and GSK-3 beta can also induce Alzheimer's disease-like phosphorylation of tau in mammalian cells, we studied the phosphorylation status of tau in primary neuronal cultures and transfected COS cells following changes in the activities of MAP kinase and GSK-3. RESULTS: Activating MAP kinase in cultures of primary neurons or transfected COS cells expressing tau isoforms did not increase the level of phosphorylation for any PHF-tau epitope investigated. But elevating GSK-3 activity in the COS cells by co-transfection with GSK-3 alpha or GSK-3 beta decreased the electrophoretic mobility of tau so that it resembled that of PHF-tau, and induced reactivity with eight PHF-tau-selective monoclonal antibodies. CONCLUSIONS: Our data indicate that GSK-3 alpha and/or GSK-3 beta, but not MAP kinase, are good candidates for generating PHF-type phosphorylation of tau in Alzheimer's disease. The involvement of other kinases in the generation of PHFs cannot, however, be eliminated. Our results suggest that aberrant regulation of GSK-3 may be a pathogenic mechanism in Alzheimer's disease.

Alzheimer Disease↗
PubMed1993

Postnatal psychiatric illness: the impact on partners.

Out of 24 spouses of women with postnatal psychiatric illness admitted to a mother and baby unit over 12 months, 12 were found to be psychiatrically ill, as defined by RDC or DSM-III criteria. The rate of psychiatric disorder was higher in these men than in a control group of men whose partners remained well after childbirth and a group of men whose partners were admitted to a psychiatric hospital with non-puerperal illness. The onset of psychiatric illness in the men typically followed admission of their wives to the mother and baby unit. Other associations with illness in the man were a history of chronic social problems, previous psychiatric episodes, and a poor relationship with his own father.

Adult↗
PubMed1992

Cytoskeletal abnormalities in Alzheimer's disease.

A fundamental process in the pathogenesis of Alzheimer's disease (AD) is the breakdown of the cytoskeleton. The microscopic manifestation of this--neurofibrillary tangles--is described. Tangles are formed from paired helical filaments (PHF), in turn constructed from abnormally phosphorylated Tau proteins. Recent investigations on the process of Tau phosphorylation and possible links between amyloid deposition and tangle formation are reviewed.

Alzheimer Disease↗