Neuropathology of cognitive decline in Lewy body disease

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390248
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokyo Metropolitan Institute of Gerontology
• Principal Investigator: MURAYAMA Shigeo Tokyo Metropolitan Institute of Gerontology, 東京都健康長寿医療センター研究所, 研究部長 (50183653)
• Co-Investigator(Kenkyū-buntansha): SAITO Yuko 独立行政法人国立精神・神経医療研究センター, 臨床検査部, 室長 (60344066)
• Co-Investigator(Renkei-kenkyūsha): ISHII Kenji 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (10231135) ; HATSUTA Hiroyuki 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (60469963)
• Project Period (FY): 2008 – 2010

Research Abstract

We studied to identify anatomic substrates to explain dementia in Lewy body disease. Neuropathologically, consecutive autopsy cases were immunocytochemically studied for difference in Lewy body dementia (dementia with Lewy bodies : DLB and Parkinson disease with dementia) Parkinson disease without dementia. Neuroradiologically, PET scans for dopamine transporter (^<11>C-CFT), glucose metabolism (^<18>F-FDG) and amyloid (^<11>C-PIB) were comparatively examined.
Overall, 99 autopsy cases with diagnosis DLB, PDD or PD were recruited for this study. All the cases were immunocytochemically screened for anti-Abta (11-28), phosphorylated tau (AT8) and phosphorylated alpha-synuclein (psyn#64). From 2008-2010, three more autopsy cases were newly recruited for this study. Substrates of DLB/PDD-PD consisted of neocortical plaque as well as alpha-sunuclein deposition in neocortex, limbic system and caudate nucleus. Substrates of Lewy body dementia with neocortical amyloid positive and negative case s consisted of limbic and necortical alpha-synuclein but not striatal alpha-synuclein. Twenty three cases of pure Lewy body dementia with sufficient alpha-synuclein deposition without significant Abeta and tau deposition were selected from consecutive 8344 autopsy cases and 20 were classified into limbic form and 3 into neocortical form. These pure Lewy body cases lacked striatal Abeta deposition.
About clinical PET studies, three each of DLB/PDD and PD cases were recruited for the study. Decreased ^<11>C-CFT uptake in caudate nucleus of DLB/PDD patients were confirmed. About ^<11>C-PIB PET scans, the three PD cases lacked cortical uptake at all and two out of three PDD/DLB cases also lacked cortical uptake. Thus, the correlation between striatal ^<11>C-CFT uptake and ^<11>C-PIB could not be calculated.
Our data confirmed anatomical substrate for dementia in Lewy body disease consisted of deposition of alpha-synuclein in limbic and neocortical structure. Our study also highlighted deposition of alpha-synuclein in caudate nucleus as strategic target for Lewy body dementia Our study could not confirm the previous reports that striatal deposition of Abeta is responsible for Lewy body dementia.
Pathogenesis of alpha-synuclein deposition and decreased DAT scan in caudate nucleus in Lewy body dementia is yet to be clarified.

Research Products

• [Journal Article] Validation of cardiac 123I-MIBG scintigraphy in patients with Parkinson's disease who were diagnosed with dopamine PET. (2010)
  • Author(s): Ishibashi K, Saito Y, Murayama S, Kanemaru K, Oda M, Ishiwata K, Mizusawa H, Ishii K
  • Journal Title: Eur J Nucl Med Mol Imaging 37 Pages: 3-11
• [Journal Article] Cerebrospinal fluid metabolite and nigrostriatal dopaminergic function in Parkinson's disease. (2010)
  • Author(s): Ishibashi K, Kanemaru K, Saito Y, Murayama S, Oda K, Ishiwata K, Mizusawa H, Ishii K
  • Journal Title: Acta Neurol Scand 122 Pages: 46-50
• [Journal Article] α-Synuclein accumulation in skin nerve fibers revealed by skin biopsy in pure autonomic failure. (2010)
  • Author(s): Shishido T, Ikemura M, Obi T, Yamazaki K, Terada T, Sugiura A, Saito Y, Murayama S, Mizoguchi K
  • Journal Title: Neurology 74 Pages: 608-610
• [Journal Article] Neuropathological asymmetry in argyrophilic grain disease. (2010)
  • Author(s): Adachi T, Saito Y, Hatsuta H, Funabe S, Tokumaru AM, Ishii K, Arai T, Sawabe M, Kanemaru K, Miyashita A, Kusano R, Nakashima K, Murayama S
  • Journal Title: J Neuropath Exp Neurol 69 Pages: 737-744
• [Journal Article] Prospective 10-year surveillance of human prion diseases in Japan Brain (2010)
  • Author(s): Nozaki I, Hamaguchi T, Sanjo N, Noguchi-Shinohara M, Sakai K, Nakamura Y, Sato T, Kitamoto T, Mizusawa H, Moriwaka F, Shiga Y, Kuroiwa Y, Nishizawa M, Kuzuhara S, Inuzuka T, Takeda M, Kuroda S, Abe K, Murai H, Murayama S, Tateishi J, Takumi I, Shirabe S, Harada M, Sadakane A, Yamada M
  • Journal Title: 133 Pages: 3043-3057
• [Journal Article] Imaging-Pathologic Correlation in Corticobasal Degeneration. (2009)
  • Author(s): Tokumaru A, Saito Y, Murayama S, Kanemaru K, Sakiyama Y, Toyoda M, Yamakawa H, Terada H
  • Journal Title: Am J Neuroradiol 30 Pages: 1884-1892
• [Journal Article] Spinocerebellar ataxia type 31 is associated with "inserted" penta-nucleotide repeats containing (TGGAA)n. (2009)
  • Author(s): Sato N, Amino T, Kobayashi K, Asakawa S, Ishiguro T, Tsunemi T, Takahashi M, Matsuura T, Flanigan KM, Iwasaki S, Ishino F, Saito Y, Murayama S, Yoshida M, Hashizume Y, Takahashi Y, Tsuji S, Shimizu N, Toda T, Ishikawa K, Mizusawa H
  • Journal Title: Am J Hum Gen 85 (5) Pages: 544-557
• [Journal Article] Basophilic inclusion body disease and neuronal intermediate filament inclusion disease : a comparative clinicopathological study. (2008)
  • Author(s): Yokota O, Tsuchiya K, Terada S, Ishizu H, Uchikado H, Ikeda M, Oyanagi K, Nakano I, Murayama S, Kuroda S, Akiyama H
  • Journal Title: Acta Neuropath 115 Pages: 561-575
• [Journal Article] Presynaptic and postsynaptic nigrostriatal dopaminergic functions in multiple system atrophy. (2008)
  • Author(s): Hashimoto M, Kawasaki K, Suzuki M, Mitani K, Murayama S, Mishina M, Oda K, Kimura Y, Ishiwata K, Ishii K, Inoue K
  • Journal Title: Neuroreport 19 Pages: 145-150
• [Journal Article] Lewy body pathology involves cutaneous nerves. (2008)
  • Author(s): Ikemura M, Saito Y, Sengoku R, Sakiyama Y, Hatsuta H, Kanemaru K, Sawabe M, Arai T, Ito G, Iwatsubo T, Fukayama M, Murayama S
  • Journal Title: J Neuropath Exp Neurol 67 Pages: 945-953
• [Journal Article] Development of a high-throughput microarray-based resequencing system for neurological disorders and its application to molecular genetics of amyotrophic lateral sclerosis. (2008)
  • Author(s): Takahashi Y, Seki N, Ishiura H, Mitsui J, Matsukawa T, Kishino A, Onodera O, Aoki M, Shimozawa N, Murayama S, Itoyama Y, Suzuki Y, Sobue G, Nishizawa M, Goto, J, Tsuji S
  • Journal Title: Arch Neurol 65 Pages: 1326-1332
• [Journal Article] The incidence and extent of Lewy-body related alpha- synucleinopathy in human aging olfactory bulb. (2008)
  • Author(s): Sengoku R, Saito Y, Ikemura M, Sakiyama Y, Hatsuta H, Kanemaru K, Sawabe M, Arai T, Mochizuki H, Inoue K, Murayama S
  • Journal Title: J Neuropath Exp Neurol 67 Pages: 1072-1083
• [Presentation] Olfactory epithelium in Lewy body disease. (2010)
  • Author(s): Funabe S, Saito Y, Hatsuta H, Sugiyama M, Murayama S
  • Organizer: 86th Annual Meeting of American Association of Neuropathologists
  • Place of Presentation: Philadelphia, PA
  • Year and Date: 20100610-20100613
• [Remarks] ホームページ等
  • URL: www.mci.gr.jp/BrainBank/