BRAIN and NERVE－神経研究の進歩68巻4号

2016年04月発行

増大特集 治せる認知症

アルツハイマー病根本治療薬の開発—治せる認知症を目指して

著者： 秋山治彦¹

所属機関： ¹横浜市立脳卒中・神経脊椎センター臨床研究部

ページ範囲：P.463 - P.472

文献概要

アルツハイマー病の根本治療薬開発においては，認知症が出現する前に発見し，その段階で病理プロセスを止めて認知症に至らないようにすることが求められる。PETを用いたアミロイドやタウのイメージング，脳脊髄液バイオマーカーなどの進歩により発症前診断は実現したが，そのプレクリニカル期における病態修飾薬の治験を繰り返し行い，多数の候補薬をスクリーニングして目標を達成するためには，効率のよい参加者リクルートのしくみが求められる。

参考文献

1)Braak H, Braak E: Neuropathological staging of Alzheimer-related changes) Acta Neuropathol 82: 239-259, 1991

2)McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, et al: Consortium on DLB. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65: 1863-1872, 2005

3)Crary JF, Trojanowski JQ, Schneider JA, Abisambra JF, Abner EL, et al: Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 128: 755-766, 2014

4)Jack CR Jr: Individuals with imaging/biomarker evidence of Alzheimer's disease (AD)-like neurodegeneration without β-amyloidosis have been labeled “suspected non-Alzheimer's pathophysiology (SNAP)” Acta Neuropathol 128: 773-776, 2014

5)Duyckaerts C, Braak H, Brion JP, Buée L, Del Tredici K, et al: PART is part of Alzheimer disease. Acta Neuropathol 129: 749-756, 2015

6)Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, et al: A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488: 96-99, 2012

7)Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, et al: Long-term eff ects of Aβ42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial. Lancet 372: 216-223, 2008

8)Wischik CM, Staff RT, Wischik DJ, Bentham P, Murray AD, et al: Tau aggregation inhibitor therapy: an exploratory phase 2 study in mild or moderate Alzheimer's disease. J Alzheimers Dis 44: 705-720, 2015

9)Baddeley TC, McCaffrey J, Storey JM, Cheung JK, Melis V, et al: Complex disposition of methylthioninium redox forms determines efficacy in tau aggregation inhibitor therapy for Alzheimer's disease. J Pharmacol Exp Ther 352: 110-118, 2015

10)Pedersen JT, Sigurdsson EM: Tau immunotherapy for Alzheimer's disease. Trends Mol Med 21: 394-402, 2015

11)Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, et al: The Consortium to Establish a Regsitry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathological assessment of Alzheimer's disease. Neurology 41: 479-486, 1991

12)Consensus recommendation for the postmortem diagnosis of Alzheimer's disease. The National Institute on Aging, and Reagan Institute working group on diagnostic criteria for the neuropathological assessment of Alzheimer's disease. Neurobiol Aging 18 (Suppl 4): S1-S2, 1997

13)Hymana BT, Phelps CH, Beach TG, Bigio EG, Cairnse NJ, et al: National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement 8: 1-13, 2012

14)Weiner MW, Veitch DP, Aisen PS, Beckett LA, Cairns NJ, et al: Update of the Alzheimer's Disease Neuroimaging Initiative: A review of papers published since its inception. Alzheimers Dement. 11: e1-e120, 2015

15)Jack CR Jr., Albert MS, Knopman DS, McKhann GM, Sperling RA, et al: Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7: 257-262, 2011

16)McKhann GM, Knopman DS, Chertkowd H, Hyman BT, Jack CR Jr. et al: The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7: 263-269, 2011

17)Alberta MS, DeKoskyb ST, Dickson D, Dubois B, Feldman HH, et al: The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement 7: 270-279, 2011

18)Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, et al: Towards defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging and the Alzheimer Association Workgroup. Alzheimers Dement 7: 280-292, 2011

19)Jack CR Jr, Knopman DS, Jagust WJ, Petersen RC, Weiner MW, et al: Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol 12: 207-216, 2013

20)Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, et al: Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med 367: 795-804, 2012

21)Sperling R, Mormino E, Johnson K: The evolution of preclinical Alzheimer's disease: implications for prevention trials. Neuron 84: 608-622, 2014

22)Reiman EM, Langbaum JB, Tariot PN, Lopera F, Bateman RJ, et al: CAP-advancing the evaluation of preclinical Alzheimer disease treatments. Nat Rev Neurol 12: 56-61, 2016

23)Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, et al: A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet 385: 2255-2263, 2015