1996 Fiscal Year Annual Research Report

Alzheimer病における生物学的早期診断マーカーの確立

Research Project

Project/Area Number	08680832
Research Category	Grant-in-Aid for Scientific Research (C)
Research Institution	Tohoku University
Principal Investigator	荒井啓行東北大学, 医学部・附属病院, 助手 (30261613)
Keywords	Alzheimer病 / 脳脊髄液 / タウ蛋白 / 診断マーカー / パーキンソン病 / 運動ニューロン病
Research Abstract	東北大学老人科および米国Graduate Hospital (フィラデルフィア市)に外来通院または入院中のAD患者87名(平均年齢73.8±8.8歳),パーキンソン病(PD)患者13名(68.4±10.0歳),運動ニューロン病(MND)患者12名(66.2±8.2歳),進行性核上性麻痺(PSP)患者5名(66.8±5.0歳),脳血管障害(CVD)患者21名(67.8±10.6歳),AIDS患者4名(39.0±4.7歳),髄膜炎または脳炎(髄膜炎/脳炎)患者35名(33.9±14.8歳),てんかん患者6名(48.8±23.1歳),上記以外の神経疾患患者(他群)18名(57.7±16.0歳),および正常コントロール22名(48.2±20.1歳)を対象とした(計223名)。87名のAD患者の内訳は,1)男性35名,女性52名;2)65歳未満発症のearly-onset AD 28名(うち家族歴を有するもの5名),65歳以降発症のlate-onset AD 54名(うち家族歴を有するもの5名),発症年齢不詳5名;3)本邦のAD患者67名,米国のAD患者20名(白人16名,黒人3名,Native American 1名)である。CVD群は,すべて慢性期の脳血管障害患者を対象とし,髄膜炎/脳炎群では,タンパク・細胞数増加のもっとも著しい時期のCSFを分析対象とした。他群の内訳は,筋疾患患者4名,Creutzfeld-Jacob病患者3名,正常圧水頭症患者3名,多発性硬化症患者3名,急性小脳炎患者1名,神経梅毒患者1名,慢性炎症性脱髄性多発根神経炎患者1名,Bell麻痺患者1名,横断性脊髄炎患者1名およびビタミンB_<12>欠乏症患者1名である。 22名の正常コントロール群におけるCSF-tau値は,10.6±8.6Pg/ml(平均±標準偏差)であった。CSF-tau値は,加齢とともに緩徐に増加する傾向が見られた(Y=0.215X+3.43,γ=0.541, P=0.017)。これら正常者におけるCSF-tauは、髄液総蛋白量の約2×10^<-6>%を占めた。一方,図2に示すようにCSF-tau値はAD群で78.0±44.2Pg/ml, PD群で19.1±8.5Pg/ml, MND群で26.3±21.2Pg/ml, PSP群で20.1±11.6Pg/ml, CVD群で24.4±31.4Pg/ml, AIDS群で49.6±37.6Pg/ml,髄膜炎/脳炎群で30.1±43.4Pg/ml,てんかん群で14.2±10.6Pg/ml,他群で35.7±52.5Pg/mlであった(df=9,F-value 12.19, P<0.0001)。AD以外の神経疾患患者全体におけるCSF-tau値は,27.8±38.7Pg/mlでありAD群と比して有意な相違がみられた(P<0.001)。また,AD以外の神経疾患の中で,MND (1例), CVC (2例), AIDS (2例),髄膜炎/脳炎(4例), Creutzfeldt-Jacob病(3例),正常圧水頭症(1例)およびビタミンB_<12>欠乏症(1例)においてCSF-tauの高値が見られたが,これらの患者とADとの鑑別が臨床上問題となることも考えられる。血清tau値は,測定限界以下であった。

Research Products
(30 results)

All Other

All Publications (30 results)

[Publications] Usuda et al.: "Differential subcellular localigation…" J. Histochem. Cytochem.44. 13-18 (1996)
[Publications] Arai et al.: "Pupil dilatation assay by…" NeuroReport. 7. 918-920 (1996)
[Publications] Yamaguchi et al.: "Temporal Progression of hippooampal…" J. Am. Geriatr, Soc.44. 216-217 (1996)
[Publications] Higuchi et al.: "Presenilin-1 polymorphism…" Lancet. 347. 1185-1187 (1996)
[Publications] Yoneyama et al.: "Oral bygiene reduces respiratory…" Arch. Gerontol. Geriatr. 22. 11-19 (1996)
[Publications] Arai et al.: "Lack of arsociation of …" Newro clegeneration. 5. 194-195 (1996)
[Publications] Sasaki et al.: "Terminal care medical fees…" J. Am. Geriatric Soc.44. 611-612 (1996)
[Publications] Terajima et al.: "Elevated cerebrospinal fluid tau…" J. Am. Geriatr. Soc.44. 1012-013 (1996)
[Publications] Higuchi et al.: "S182 and STM2 gene mutation…" Am. J. Med. Genet.67. 429- (1996)
[Publications] Bao et al.: "Expression of apolipoprotein E…" Neuro Report. 7. 1733-1739 (1996)
[Publications] Muramatsu et al.: "α、-Antichymotrypsin gene…" J. Neural Trans.103. 1205-1210 (1996)
[Publications] Sasaki et al.: "Will aging of the population…" J. Am. Geriatr, Soc. 44. 1013-1014 (1996)
[Publications] Itabashi et al.: "ApoE ε4 allele in Alzbeimer…" Lancet. 348. 960-961 (1996)
[Publications] Kobayashi et al.: "Levo-dopa and suallowing…" Lancet. 348. 1320-1321 (1996)
[Publications] Nakagawa et al.: "High incidence of preumonia…" Arch. Intern. Med.157. 321-324 (1997)
[Publications] Higuchi et al.: "Pupillary response to tropicamide…" Exp. Neurol in press. (1997)
[Publications] Higuchi et al.: "Apolipoprotein E ε4 allele and …" Am. J. Psychiatry. (in press). (1997)
[Publications] Kosaka et al.: "The β-App717 Abhemer mutation" Neurology. (in press). (1997)
[Publications] Arai et al.: "Effect of genetic risk factors…" J. Am. Geriatr. Soc. (in press). (1997)
[Publications] Nakamra et al.: "Postural and gait disturbance…" Alzheirner's dirense and Associt. (in press). (1997)
[Publications] Kuda et al.: "Reduction of plasma glutamyl…" Biocherc, Biophys. Res. Comor. (in press). (1997)
[Publications] Obrui et al.: "Disturbel conscionsness and …" Lancet in press. (1997)
[Publications] Arai et al.: "Review : Biologrical markers…" Tohoku J. Exp. Med.179. 65-79 (1996)
[Publications] Trojanowski et al.: "Elevated leuels of cerebrospinal…" Abheimer's disease Revicus. 1. 77-83 (1996)
[Publications] Arai et al.: "Apolipoprotein E genotyping and…" Gerontology. (in press). (1997)
[Publications] Higuchi et al.: "THe apolipoprotein F gene in…" Clin, Genet. (in press). (1997)
[Publications] 荒井啓行ら: "アルツハイマー病における生物学的…" 日本老年医学会雑誌‥. 33. 669-675 (1996)
[Publications] 荒井啓行ら: "アルツハイマー病における生物学的…" 神経研究の進歩. 41. 130-139 (1997)
[Publications] 荒井啓行: "痴呆性疾患におけるApolipoproteinE" 老年期痴呆研究会誌. 9. 6-8 (1996)
[Publications] Trojanowski et al.: "Current Neurology" S. Appel Mosby year book, 21 (1996)

1996 Fiscal Year Annual Research Report

Alzheimer病における生物学的早期診断マーカーの確立

Principal Investigator

荒井 啓行 東北大学, 医学部・附属病院, 助手 (30261613)

Research Products

[Publications] Usuda et al.: "Differential subcellular localigation…" J. Histochem. Cytochem.44. 13-18 (1996)

[Publications] Arai et al.: "Pupil dilatation assay by…" NeuroReport. 7. 918-920 (1996)

[Publications] Yamaguchi et al.: "Temporal Progression of hippooampal…" J. Am. Geriatr, Soc.44. 216-217 (1996)

[Publications] Higuchi et al.: "Presenilin-1 polymorphism…" Lancet. 347. 1185-1187 (1996)

[Publications] Yoneyama et al.: "Oral bygiene reduces respiratory…" Arch. Gerontol. Geriatr. 22. 11-19 (1996)

[Publications] Arai et al.: "Lack of arsociation of …" Newro clegeneration. 5. 194-195 (1996)

[Publications] Sasaki et al.: "Terminal care medical fees…" J. Am. Geriatric Soc.44. 611-612 (1996)

[Publications] Terajima et al.: "Elevated cerebrospinal fluid tau…" J. Am. Geriatr. Soc.44. 1012-013 (1996)

[Publications] Higuchi et al.: "S182 and STM2 gene mutation…" Am. J. Med. Genet.67. 429- (1996)

[Publications] Bao et al.: "Expression of apolipoprotein E…" Neuro Report. 7. 1733-1739 (1996)

[Publications] Muramatsu et al.: "α、-Antichymotrypsin gene…" J. Neural Trans.103. 1205-1210 (1996)

[Publications] Sasaki et al.: "Will aging of the population…" J. Am. Geriatr, Soc. 44. 1013-1014 (1996)

[Publications] Itabashi et al.: "ApoE ε4 allele in Alzbeimer…" Lancet. 348. 960-961 (1996)

[Publications] Kobayashi et al.: "Levo-dopa and suallowing…" Lancet. 348. 1320-1321 (1996)

[Publications] Nakagawa et al.: "High incidence of preumonia…" Arch. Intern. Med.157. 321-324 (1997)

[Publications] Higuchi et al.: "Pupillary response to tropicamide…" Exp. Neurol in press. (1997)

[Publications] Higuchi et al.: "Apolipoprotein E ε4 allele and …" Am. J. Psychiatry. (in press). (1997)

[Publications] Kosaka et al.: "The β-App717 Abhemer mutation" Neurology. (in press). (1997)

[Publications] Arai et al.: "Effect of genetic risk factors…" J. Am. Geriatr. Soc. (in press). (1997)

[Publications] Nakamra et al.: "Postural and gait disturbance…" Alzheirner's dirense and Associt. (in press). (1997)

[Publications] Kuda et al.: "Reduction of plasma glutamyl…" Biocherc, Biophys. Res. Comor. (in press). (1997)

[Publications] Obrui et al.: "Disturbel conscionsness and …" Lancet in press. (1997)

[Publications] Arai et al.: "Review : Biologrical markers…" Tohoku J. Exp. Med.179. 65-79 (1996)

[Publications] Trojanowski et al.: "Elevated leuels of cerebrospinal…" Abheimer's disease Revicus. 1. 77-83 (1996)

[Publications] Arai et al.: "Apolipoprotein E genotyping and…" Gerontology. (in press). (1997)

[Publications] Higuchi et al.: "THe apolipoprotein F gene in…" Clin, Genet. (in press). (1997)

[Publications] 荒井啓行ら: "アルツハイマー病における生物学的…" 日本老年医学会雑誌‥. 33. 669-675 (1996)

[Publications] 荒井啓行ら: "アルツハイマー病における生物学的…" 神経研究の進歩. 41. 130-139 (1997)

[Publications] 荒井啓行: "痴呆性疾患におけるApolipoproteinE" 老年期痴呆研究会誌. 9. 6-8 (1996)

[Publications] Trojanowski et al.: "Current Neurology" S. Appel Mosby year book, 21 (1996)

荒井啓行東北大学, 医学部・附属病院, 助手 (30261613)