ABSTRACT
BACKGROUND: Understanding what distinguishes the suicide of individuals reported missing (missing-suicides) from those of individuals not reported missing (other-suicides) may have preventative and/or operational utility and inform our knowledge of suicide.AimsTo assess whether specific epidemiological, sociodemographic or circumstantial characteristics differ between individuals reported missing and those not reported missing who take their own life. METHOD: Content analysis of Scottish Police Death Reports, detailing 160 suicides/undetermined deaths over a 3-year period in the North-East of Scotland. RESULTS: Those in the missing-suicide group were more likely to be older but did not differ from the other-suicide group on any other epidemiological or sociodemographic characteristics. Individuals in the other-suicide group were more likely to be found inadvertently by people known to them. The missing-suicide group took longer to find and were more likely to be located in natural outdoor locations by police/searchers or members of the public. CONCLUSIONS: Individuals who die by suicide and who are reported as a missing person differ from those not reported as missing in terms of factors relating to location and how they are found but not epidemiological or sociodemographic characteristics.Declaration of interestNone.
ABSTRACT
Familial Danish dementia (FDD) is pathologically characterized by widespread cerebral amyloid angiopathy (CAA), parenchymal protein deposits, and neurofibrillary degeneration. FDD is associated with a mutation of the BRI2 gene located on chromosome 13. In FDD there is a decamer duplication, which abolishes the normal stop codon, resulting in an extended precursor protein and the release of an amyloidogenic fragment, ADan. The aim of this study was to describe the major neuropathological changes in FDD and to assess the distribution of ADan lesions, neurofibrillary pathology, glial, and microglial response using conventional techniques, immunohistochemistry, confocal microscopy, and immunoelectron microscopy. We showed that ADan is widely distributed in the central nervous system (CNS) in the leptomeninges, blood vessels, and parenchyma. A predominance of parenchymal pre-amyloid (non-fibrillary) lesions was found. Abeta was also present in a proportion of both vascular and parenchymal lesions. There was severe neurofibrillary pathology, and tau immunoblotting revealed a triplet electrophoretic migration pattern comparable with PHF-tau. FDD is a novel form of CNS amyloidosis with extensive neurofibrillary degeneration occurring with parenchymal, predominantly pre-amyloid rather than amyloid, deposition. These findings support the notion that parenchymal amyloid fibril formation is not a prerequisite for the development of neurofibrillary tangles. The significance of concurrent ADan and Abeta deposition in FDD is under further investigation.
Subject(s)
Amyloid beta-Peptides/metabolism , Amyloidosis/metabolism , Brain Diseases/metabolism , Dementia/genetics , Dementia/metabolism , Adult , Amyloidosis/pathology , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/metabolism , Benzothiazoles , Blood Vessels/metabolism , Brain Diseases/pathology , Coloring Agents , Congo Red , Dementia/pathology , Denmark , Female , Fluorescent Dyes , Glial Fibrillary Acidic Protein/metabolism , Histocompatibility Antigens Class II/metabolism , Humans , Immunoblotting , Immunohistochemistry , Male , Microscopy, Electron , Microscopy, Immunoelectron , Middle Aged , Pedigree , Staining and Labeling , Thiazoles , tau Proteins/metabolismABSTRACT
The increased production of amyloid beta-peptide (Abeta) in Alzheimer's disease is acknowledged to be a key pathogenic event. In this study, we examined the response of primary human and rat brain cortical cultures to Abeta administration and found a marked increase in the tyrosine phosphorylation content of numerous neuronal proteins, including tau and putative microtubule-associated protein 2c (MAP2c). We also found that paired helical filaments of aggregated and hyperphosphorylated tau are tyrosine phosphorylated, indicating that changes in the phosphotyrosine content of cytoplasmic proteins in response to Abeta are potentially an important process. Increased tyrosine phosphorylation of cytoskeletal and other neuronal proteins was specific to fibrillar Abeta(25-35) and Abeta(1-42). The tyrosine phosphorylation was blocked by addition of the Src family tyrosine kinase inhibitor 4-amino-5-(4-chlorophenyl)-7(t-butyl)pyrazol(3,4-d)pyramide (PP2) and the phosphatidylinositol 3-kinase inhibitor LY 294002. Tyrosine phosphorylation of tau and MAP2c was concomitant with an increase in the tyrosine phosphorylation and subsequent putative activation of the non-receptor kinase, focal adhesion kinase (FAK). Immunoprecipitation of Fyn, a member of the Src family, from Abeta(25-35)-treated neurons showed an increased association of Fyn with FAK. Abeta treatment of cells also stimulated the sustained activation of extracellular regulated kinase-2, which was blocked by addition of PP2 and LY 294002, suggesting that FAK/Fyn/PI3-kinase association is upstream of mitogen-activated protein (MAP) kinase signaling in Abeta-treated neurons. This cascade of signaling events contains the earliest biochemical changes in neurons to be described in response to Abeta exposure and may be critical for subsequent neurodegenerative changes.