2005 Fiscal Year Final Research Report Summary
Neuropathological study on atypical Alzheimer's disease and diffuse neurofibrillary tangles with calcification (DNTC)
| Project/Area Number |
15591227
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Okayama University |
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Principal Investigator |
TERADA Seishi Okayama University, University Hospital, Lecturer, 医学部・歯学部附属病院, 講師 (20332794)
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| Project Period (FY) |
2003 – 2005
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| Keywords | Alzheimer's disease / atypical Alzheimer's disease / diffuse neurofibrillary tangles with calcification / neuropathology / cotton wool plaque / schizophrenia / cyclooxygenase-2 / exon-3 |
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| Research Abstract |
1.
We describe three cases of early- and one of late-onset Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history. In conclusion, (1)a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2)the deposition pattern of Abeta40 and Abeta42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3)Abeta deposition can result in development of dementia without tau pathology, and (4)CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving alpha-synuclein and NAC deposition.
2.
Recently, a prospective double-blind study demonstrated that supplementary treatment with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, produced significantly greater improvement in scores on the Positive and Negative Syndrome Scale (PANSS) and on all subscales during the acute phase in patients with schizophrenia compared with risperidone alone therapy. Quantitative immunohistochemical analysis demonstrated that neuronal COX-2 expression was significantly up-regulated in each CA1-4 region in Alzheimer's disease compared with controls. In contrast, COX-2 expression was not up-regulated in any subdivision of the hippocampus in the schizophrenia group. These results suggest that celecoxib may affect the pathophysiology of schizophrenia through COX-2-independent actions rather than by inhibiting activity of up-regulated COX-2 protein.
3.
We performed an immunohistochemical study on tau-positive structures in neurodegenerative diseases, to clarify whether tau with the exon 3 insert was present in abnormal tau-positive structures. Abnormally phosphorylated tau containing the exon 3 insert is present in both PSP and CBD brain. Although most intraglial inclusions were negative for anti-E3 Ab, a few were positive. Therefore, tau isoforms containing the exon 3 insert are expressed at low levels in glial cells.
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