Conference Abstract| February 01 2000 α-Synuclein in Alzheimer's Disease and Multiple System Atrophy S. Gillet; S. Gillet 1Dept of Neuroscience, Institute of Psychiatry, London SE5 8AF Search for other works by this author on: This Site PubMed Google Scholar T. Revesz; T. Revesz 2Dept of Neuropathology, Institute of Neurology, London WC1N 1PJ, UK Search for other works by this author on: This Site PubMed Google Scholar S.E. Daniel; S.E. Daniel 2Dept of Neuropathology, Institute of Neurology, London WC1N 1PJ, UK Search for other works by this author on: This Site PubMed Google Scholar B.H. Anderton; B.H. Anderton 1Dept of Neuroscience, Institute of Psychiatry, London SE5 8AF Search for other works by this author on: This Site PubMed Google Scholar D.P. Hanger D.P. Hanger 1Dept of Neuroscience, Institute of Psychiatry, London SE5 8AF Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (2000) 28 (1): A33. https://doi.org/10.1042/bst028a033 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation S. Gillet, T. Revesz, S.E. Daniel, B.H. Anderton, D.P. Hanger; α-Synuclein in Alzheimer's Disease and Multiple System Atrophy. Biochem Soc Trans 1 February 2000; 28 (1): A33. doi: https://doi.org/10.1042/bst028a033 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search This content is only available as a PDF. © 2000 Biochemical Society2000 Article PDF first page preview Close Modal You do not currently have access to this content.

OBJECTIVES Dementia in Alzheimer’s disease correlates closely with loss of neocortical synapses. Similar synaptic loss has been shown in patients whose Alzheimer’s disease is also associated with neocortical and brain stem Lewy bodies. The aim was to determine if dementia in Lewy body disease was associated with diminished concentrations of midfrontal cortex synaptophysin. METHODS An immunobinding assay was used to measure synaptophysin in postmortem samples of midfrontal cortex from 89 patients with Alzheimer’s disease (ages 59–100, mean 79), 22 with combined Lewy body disease and Alzheimer’s disease (ages 69–103, mean 79), 15 demented patients with “pure” Lewy body disease (ages 57–80, mean 74), nine with neocortical and brain stem Lewy bodies who had Parkinson’s disease but were not demented (ages 68–85, mean 79), and 20 neurologically normal controls (ages 58–89, mean 75). The diagnosis was confirmed in all cases by detailed neuropathological examination of the contralateral hemibrain. Seven of the patients in the pure Lewy body disease with dementia group had initially presented with parkinsonism and eight with dementia. RESULTS Synaptophysin concentrations (arbitrary units (AU)/μg) in patients with Alzheimer’s disease (mean 79 (SD 28)) or combined Lewy body disease and Alzheimer’s disease (mean 83 (SD 33)) were significantly lower than in controls (mean 115 (SD 29)) (p=0.002). Synaptophysin concentrations in demented patients with pure Lewy body disease (mean 106 SD 39) and patients with Lewy body disease who were not demented (mean 101 (SD 18)) did not differ significantly from control values or from each other. CONCLUSION Loss of midfrontal cortex synapses probably contributes to dementia in Lewy body disease when Alzheimer’s disease is also present but not to the dementia of pure Lewy body disease.

Cerebral cortical Lewy bodies occur in a spectrum of clinical syndromes including Parkinson's disease (PD) with and without dementia, and dementing conditions clinically resembling Alzheimer's disease with few or without parkinsonian features. It is unclear whether these conditions are variants of one disease process or represent pathogenetically distinct entities. Here we compared the cortical pathology in post mortem brains of three groups representing the predominant clinical phenotypes of Lewy body disease, including 27 non-demented cases of PD, 23 demented PD cases, and 11 cases of Lewy body disease who initially presented with dementia and showed only limited features of parkinsonism during the course of their illness. In addition to neuropathology, computer-assisted histoblot analysis was used to assess cortical amyloid beta-peptide deposition. There was wide overlap of the pathomorphometric features between the two groups of demented cases. It appears that substantial cortical Alzheimer-type pathology present in most demented cases contributes significantly to the development of dementia in Lewy body disease.

The publisher can give no guarantee for information about drug dosage and application thereof contained in this book.In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature.The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.

To date, five single base pair changes of the mitochondrial DNA have been reported to occur either exclusively or with increased frequency in Caucasian patients with Parkinson's disease (PD) and it has been postulated that these mutations might be causally related to the observed inhibition of mitochondrial respiratory chain function in PD. To evaluate these findings, we analysed the frequency of all five polymorphisms in 100 cases of pathologically proven cases of PD. We were either unable to detect the previously described polymorphisms in our series or found them to be present with the same frequency among controls. Our data do not support the hypothesis of an involvement of the mitochondrial DNA in the pathogenesis of PD.

The histoblot immunostaining technique for locating and characterizing amyloidogenic proteins was used to obtain information about the relationship of cerebral ischemia/hypoxia to the accumulation of amyloid beta protein (A beta). We investigated brains of 131 subjects (ages 25-94 years, mean 72 years). Three distribution patterns of A beta immunoreactivity were identified: (1) colocalization with diffuse and neuritic plaques of Alzheimer's disease (AD) and aging; (2) diffuse punctuate deposits in the cerebral cortex in association with small vessel cerebral vascular disease ; and (3) cerebral cortical accumulation localized to arterial boundary zones and other regions susceptible to ischemic/hypoxic injury designated "stress-induced deposits" (SID). SID were not identified in tissue sections by immunohistochemical, Congo red or Bielschowsky silver techniques; no histological abnormalities were present in adjacent formalin-fixed tissue sections, SID occurred in subjects with histories of cerebral ischemia, and severe orthostatic hypotension. There was also an association with aging in general and with the incidence of neuritic plaques specifically. These latter findings are consistent with the hypothesis that brain ischemia/hypoxia plays a role in the pathogenesis of AD.

Die Bedeutung der kraniellen Computertomographie (CT) in der Diagnostik der Multisystem Atrophie (MSA) ist bislang nicht systematisch untersucht worden. Die Interpretation vorüegender Studien wird durch heterogene Krankheitsgruppen erschwert (Staal et al. 1990; Wessel et al. 1993). Insbesondere ist die Häufigkeit von Normalbefunden bei Patienten mit klinisch wahrscheinlicher MS A unbekannt.

In this article we describe the neuropathological changes in three patients with neuroacanthocytosis and review the neuropathology of the other eight cases reported in the literature. Macroscopically the brains showed enlargement of the lateral ventricles, especially the frontal horns. The most severely and consistently affected brain areas were the caudate nucleus and putamen, which were atrophic and showed by light microscopy marked neuronal loss and gliosis. Small and medium‐sized striatal neurons were particularly depleted. The globus pallidus was almost as severely involved as the striatum. In some cases the thalamus, substantia nigra, and anterior horns of the spinal cord showed pathology, mainly neuronal loss and mild gliosis. Brain areas with no pathology included the subthalamic nucleus, cerebral cortex, cerebellum, pons, and medulla. The preservation of these areas may help in the neuropathological distinction of neuroacanthocytosis from Huntington's disease.

We counted nerve cells in different subregions of the substantia nigra in three patients with neuroacanthocytosis and compared the results with those of age-matched Parkinson's disease and control patients. Two patients with neuroacanthocytosis and clinical parkinsonism in life had a reduced neuronal density in the substantia nigra, while in a third patient without parkinsonism, this number was at the lower limit of the control range. In neuroacanthocytosis with parkinsonism and in Parkinson's disease, the ventrolateral region of the substantia nigra was most severely affected, although in neuroacanthocytosis cases, nigral neuronal loss was more widespread.

The UK Parkinson's Disease Society Brain Bank receives tissue from patients with Parkinson's disease and a variety of different movement disorders. Half of the brain is used for full neuropathological examination prior to allocation for specific research projects. Clinical misdiagnosis occurs in a significant proportion of cases and clinico-pathological correlation provides valuable information for disease recognition. With the expanding number of other specialist brain banks there is a need for agreement on diagnostic criteria. Furthermore, awareness of different methods of tissue handling is essential.