Department of Aging Neurobiology

1. Molecular mechanisms underlying the accumulation of amyloid-β and tau, leading to neurodegeneration.
2. Mechanisms how non-genetic risk factors, such as diabetes and aging, and genetic risk factors, such as APOE genotype, promote dementia.
3. The relationship between these genetic and non-genetic risk factors.
4. Research with the goal of delivering relief to patients (e.g., Our original exercise method & Cog-map)
5. Development of the next-generation therapeutics.

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Original Articles:

Mitsuru Shinohara, Hiroyuki Momota, Tsuyoshi Saito, Chisako Takenobu, Kensaku Kasuga, Ghupurjan Gheni, Kaori Kawai, Maho Morishima, Yuko Saito, Akihiro Shindo, Fumihiko Yasuno, Takeshi Ikeuchi, Akio Fukumori, Naoyuki Sato
CCN1/Cyr61 associates with β-amyloid levels in human cerebrospinal fluids
iScience.2026 Jun 19;29(6);116244. doi: 10.1016/j.isci.2026.116244

Mitsuru Shinohara*, Ghupurjan Gheni, Kaori Kawai, Maho Morishima, Shigeo Murayama, Yuko Saito, Guojun Bu, Naoyuki Sato
Coordinated regional association of cathepsins and dipeptidyl peptidases with N-truncated Abeta42, Abeta40, and tau in Alzheimer's brain
Acta Neuropathol Commun. 2025 Dec 31;14(1):31. doi: 10.1186/s40478-025-02146-1 

Riki Maruyama, Akio Fukumori, Satoru Funamoto, Ken Okada, Shoshin Akamine, Kanta Yanagida, Mitsuru Shinohara, Naoyuki Sato, Masayasu Okochi, Takashi Kudo, Harald Steiner
γ-Secretase exosites as targets for substrate-selective lowering of Aβ generationStructure. 2026 Feb 5;34(2):363-374.e4. doi: 10.1016/j.str.2025.11.010

Hirobumi Tada, Mitsuru Shinohara, Asuka Teramoto, Shosuke Satake, Janina Krell-Roesch, Shoya Matsumoto, Minoru Yamada, Tomomi Satoh, Reo Kawano, Keisuke Suzuki, Izumi Kondo, Masahiro Akishita, Hidenori Arai, Yonas E. Geda, Hirotaka Watada, Naoyuki Sato*
MyEveryCise: A method for everyday exercise using “an activity of daily living” as a cue
Journal of Alzheimer's Disease. First published online October 17, 2025;108(3):1034–1039. doi: 10.1177/13872877251385170

Shoya Matsumoto, Tomomi Satoh, Mitsuru Shinohara, Reo Kawano, Keisuke Suzuki, Janina Krell-Roesch, Michio Ide, Hirotaka Watada, Masahiro Akishita, Hidenori Arai, Izumi Kondo, Yonas E. Geda, Naoyuki Sato
​Development of a modified Japanese version of questionnaires to assess physical and cognitively stimulating activities
JMA Journal. April 28, 2025 ;8(2):498-505. doi: 10.31662/jmaj.2024-0153

Ricardo Aurélio Carvalho Sampaio, Yukiko Nishita, Chikako Tange, Shu Zhang, Mitsuru Shinohara, Mana Tateishi, Kanae Furuya, Sayaka Kubota, Priscila Yukari Sewo Sampaio, Naoyuki Sato, Hiroshi Shimokata, Hidenori Arai, Rei Otsuka
Interactive Associations of Age, Apolipoprotein E ε4 Gene, Physical Activity, and Physical Functioning on Processing Speed
J Am Med Dir Assoc.  2025 Nov;26(11):105489. doi: 10.1016/j.jamda.2025.105489

Ghupurjan Gheni, Mitsuru Shinohara, Masami Masuda-Suzukake, Akihiko Shindo, Atsushi Watanabe, Kaori Kawai, Guojun Bu, Hidekazu Tomimoto, Masato Hasegawa, Naoyuki Sato
Cerebral hypoperfusion reduces tau accumulation
Annals of Clinical and Translational Neurology.2025 Jan;12(1):69-85. doi: 10.1002/acn3.52247

Song Y, Dai CL, Shinohara M, Chyn Tung Y, Zhou S, Huang WC, Seffouh A, Luo Y, Willadsen M, Jiao Y, Morishima M, Saito Y, Koh SH, Ortega J, Gong CX, Lovell JF.
A pentavalent peptide vaccine elicits Abeta and tau antibodies with prophylactic activity in an Alzheimer's disease mouse model.
Brain Behav Immun. 2024 Aug 12;122:185-201. doi: 10.1016/j.bbi.2024.08.028.

Hidehisa D. Yamagata , Hiroyasu Akatsu, Tomoya Fukuoka, Akito Wake, Ichiro Watanabe, Naoto KImura, Tetsuro Miki, Kazuo Kamada, Tatsuhiko Miyazaki, Takayuki Yamamoto, Akira Hori, Naoyuki Sato, Maya Mimuro, Mari Yoshida & Yoshio Hashizume
Novel insights into presenilin 1 mutation associated with a distinctive dementia phenotype and cotton wool plaques.
Neurol Sci. 2024 Oct;45(10):4829-4835. doi: 10.1007/s10072-024-07537-1.

Kikuchi M, Miyashita A, Hara N, Kasuga K, Saito Y, Murayama S, Kakita A, Akatsu H, Ozaki K, Niida S, Kuwano R, Iwatsubo T, Nakaya A, Ikeuchi T;Alzheimer’s Disease Neuroimaging Initiative; Japanese Alzheimer’s Disease Neuroimaging Initiative.
Polygenic effects on the risk of Alzheimer's disease in the Japanese population.
Alzheimers Res Ther. 2024 Feb 27;16(1):45. doi: 10.1186/s13195-024-01414-x.

Tachibana K, Hirayama R, Sato N, Hattori K, Kato T, Takeda H, Kondoh M
Association of Plasma Claudin-5 with Age and Alzheimer Disease.
Int J Mol Sci.2024 Jan 24;25(3):1419. doi: 10.3390/ijms25031419. 

Masuda H, Mori M, Hirano S, Uzawa A, Uchida T, Muto M, Ohtani R, Aoki R, Hirano Y; Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI); Kuwabara S
Higher longitudinal brain white matter atrophy rate in aquaporin-4 IgG-positive NMOSD compared with healthy controls.
Sci Rep. 2023 Aug 3;13(1):12631. doi: 10.1038/s41598-023-38893-1.

Shinohara M, Gheni G, Hitomi J, Bu G, Sato N
APOE genotypes modify the obesity paradox in dementia
Journal of Neurology, Neurosurgery & Psychiatry 2023 Sep;94(9):670-680. doi:10.1136/jnnp-2022-331034

Kondo T, Hara N, Koyama S, Yada Y, Tsukita K, Nagahashi A, Ikeuchi T, Ishii K, Asada T, Arai T, Yamada R; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Japanese Alzheimer’s Disease Neuroimaging Initiative (J-ADNI); Inoue H
Dissection of the polygenic architecture of neuronal Aβ production using a large sample of individual iPSC lines derived from Alzheimer's disease patients.
Nat Aging. 2022 Feb;2(2):125-139. doi: 10.1038/s43587-021-00158-9.

Nishita Y, Sala G, Shinohara M, Tange C, Ando F, Shimokata H, Sato N, Otsuka R
Effects of APOEɛ4 genotype on age-associated change in cognitive functions among Japanese middle-aged and older adults: A 20-year follow-up study.
Experimental Gerontology. 2023 Jan;171:112036

Kasuga K, Kikuchi M,Tsukie T, Suzuki K, Ihara R, Iwata A, Hara N, Miyashita A, Kuwano R, Iwatsubo T, Ikeuchi T, Japanese Alzheimer’s Disease Neuroimaging Initiative
Different AT(N) profiles and clinical progression classified by two different N markers using total tau and neurofilament light chain in cerebrospinal fluid.
BMJ neurology open.2022 Aug 10;4(2):e000321.

Saji N, Murotani K, Sato N, Tsuduki T, Hisada T, Shinohara M, Sugimoto T, Niida S, Toba K, Sakurai T
Relationship between plasma neurofilament light chain, gut Microbiota, and dementia: a cross-sectional study.
Journal of Alzheimer's Disease.2022;86(3):1323-1335

Shinohara M, Hirokawa J, Shimodaira A, Tashiro Y, Suzuki K, Gheni G,  Fukumori A, Matsubara T,  Morishima M, Saito Y, Murayama S,  Sato N
ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease.
Journal of Neuropathology & Experimental Neurology.20 July, 2021;80(7):652-662. doi:10.1093/jnen/nlab047

Shinohara M, Suzuki K, Bu G, Sato N
Interaction Between APOE Genotype and Diabetes in Longevity
Journal of Alzheimer's Disease. May 29, 2021;82(2).

Suzuki K, Shinohara M, Uno Y, Tashiro Y, Gheni G, Yamamoto M, Fukumori A, Shindo A, Mashimo T, Tomimoto H, Sato N
Deletion of B-cell translocation gene 2 (BTG2) alters the responses of glial cells in white matter to chronic cerebral hypoperfusion
J Neuroinflammation. 2021 Apr 3;18(1):86.

Shinohara M, Kikuchi M, Onishi-Takeya M, Tashiro Y, Suzuki K, Noda Y, Takeda S, Mukouzono M, Nagano S, Fukumori A, Morishita R, Nakaya A, Sato N
Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease.
FASEB BioAdvances, 02 March 2021, https://faseb.onlinelibrary.wiley.com/doi/10.1096/fba.2020-00151

Shinohara M, Kanekiyo T, Tachibana M, Kurti A, Shinohara M, Yuan Fu, Jing Zhao, Xianlin Han, Patrick M Sullivan, G William Rebeck ,John D Fryer, Michael G Heckman, Guojun Bu
APOE2 is associated with longevity independent of Alzheimer's disease
eLife 2020; 9:e62199 doi: 10.7554/eLife.62199

Shinohara M, Tashiro Y, Suzuki K, Fukumori A, Guojun Bu, Sato N
Interaction between APOE genotype and diabetes in cognitive decline.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring Feb. 6,2020;12(1):e12006.

Shinohara M, Tashiro Y, Shinohara M, Hirokawa J, Suzuki K, Onishi-Takeya M, Mukouzono M, Takeda S, Saito T, Fukumori A, Saido TC, Morishita R, Sato N.
Increased levels of Aβ42 decrease the lifespan of ob/ob mice with dysregulation of microglia and astrocytes.
The FASEB Journal 2020　Feb.　34(2):2425-2435.

Yamazaki Y, Shinohara M, Yamazaki A, Ren Y, Asmann YW, Kanekiyo T, Bu G.
ApoE (Apolipoprotein E) in Brain Pericytes Regulates Endothelial Function in an Isoform-Dependent Manner by Modulating Basement Membrane Components.
Arterioscler Thromb Vasc Biol 2020 Jan.　40(1):128-144.

Zhong L, Xu Y, Zhuo R, Wang T, Wang K, Huang R, Wang D, Gao Y, Zhu Y, Sheng X, Chen K, Wang N, Zhu L, Can D, Marten Y, Shinohara M, Liu CC, Du D, Sun H, Wen L, Xu H, Bu G, Chen XF.
Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer's disease model.
Nat Commun 2019 Mar. 25;10(1):1365. doi: 10.1038/s41467-019-09118-9

Shinohara M, Shinohara M, Zhao J, Fu Y, Liu C C, Kanekiyo T, Bu G.
5-HT3 Antagonist Ondansetron Increases ApoE Secretion by Modulating the LXR-ABCA1 Pathway
Int. J. Mol. Sci. 2019, 20(6), 1488

Yamazaki Y, Shinohara M, Shinohara M, Yamazaki A, Murray ME, Liesinger AM, Heckman MG, Lesser ER, Parisi JE, Petersen RC, Dickson DW, Kanekiyo T, Bu G.
Selective loss of cortical endothelial tight junction proteins during Alzheimer's disease progression.
Brain.2019 Apr. 1;142(4):1077-1092.

Tachibana M, Holm ML, Liu CC, Shinohara M, Aikawa T, Oue H, Yamazaki Y, Martens YA, Murray ME, Sullivan PM, Weyer K, Glerup S, Dickson DW, Bu G, Kanekiyo T.
APOE4-mediated amyloid-β pathology depends on its neuronal receptor LRP1.
J Clin Invest. 2019 Mar 1;129(3):1272-1277

Zhao N, Liu CC, Van Ingelgom AJ, Linares C, Kurti A, Knight JA, Heckman MG, Diehl NN, Shinohara M, Martens YA, Attrebi ON, Petrucelli L, Fryer JD, Wszolek ZK, Graff-Radford NR, Caselli RJ, Sanchez-Contreras MY, Rademakers R, Murray ME, Koga S, Dickson DW, Ross OA, Bu G.
APOE ε2 is associated with increased tau pathology in primary tauopathy.
Nat Commun. 2018 Oct 22;9(1):4388. doi: 10.1038/s41467-018-06783-0.

Shinohara M., Koga S., Konno T., Nix J., Shinohara M., Aoki N., Das P., Parisi J. E., Petersen R. C., Rosenberry T. L., Dickson D. W., Bu G. Distinct spatiotemporal accumulation of N-truncated and full-length amyloid-β42 in Alzheimer’s disease. Brain, 140(12), 3301-3316, 2017

Wojtas A. M., Kang S. S., Olley B. M., Gatherer M., Shinohara M., Lozano P. A., Liu C. C., Kurti A., Baker K. E., Dickson D. W.,Yue M., Petrucelli L., Bu G., Carare R. O., Fryer J. D. Loss of clusterin shifts amyloid deposition to the cerebrovasculature via disruption of perivascular drainage pathways. Proc Natl Acad Sci U S A. 114(33), E6962-E6971, 2017

Zhao J. , Davis M. D., Atagi Y., Shinohara M., Graff-Radford N. R., Younkin S. G., Wszolek Z. K., Kanekiyo T., Bu G. APOE ε4/ε4 diminishes neurotrophic function of human iPSC-derived astrocytes. Human Molecular Genetics, 26(14), 2690-2700, 2017

Rogers J.T., Liu C. C., Zhao N., Wang J., Putzke T., Yang L., Shinohara M., Fryer J. D., Kanekiyo T., Bu G. Subacute ibuprofen treatment rescues the synaptic and cognitive deficits in advanced-aged mice. Neurobiology of Aging, 53, 112-121, 2017

Tachibana, M., Shinohara, M., Yamazaki, Y., Liu, C. C., Rogers, J., Bu, G., and Kanekiyo, T*. Rescuing effects of RXR agonist bexarotene on aging-related synapse loss depend on neuronal LRP1. Experimental neurology 277, 1-9, 2016.

Shinohara, M., Murray, M. E., Frank, R. D., Shinohara, M., DeTure, M., Yamazaki, Y., Tachibana, M., Atagi, Y., Davis, M. D., Liu, C. C., Zhao, N., Painter, M. M., Petersen, R. C., Fryer, J. D., Crook, J. E., Dickson, D. W., Bu, G., and Kanekiyo, T*. Impact of sex and APOE4 on cerebral amyloid angiopathy in Alzheimer's disease. Acta neuropathologica 132, 225-234, 2016.

Shinohara, M., Kanekiyo, T., Yang, L., Linthicum, D., Shinohara, M., Fu, Y., Price, L., Frisch-Daiello, J. L., Han, X., Fryer, J. D. and Bu, G*. APOE2 eases cognitive decline during Aging: Clinical and preclinical evaluations. Ann Neurol., 79: 758–774, 2016.

Sakae, N., Liu, C. C., Shinohara, M., Frisch-Daiello, J., Ma, L., Yamazaki, Y., Tachibana, M., Younkin, L., Kurti, A., Carrasquillo, M. M., Zou, F., Sevlever, D., Bisceglio, G., Gan, M., Fol, R., Knight, P., Wang, M., Han, X., Fryer, J. D., Fitzgerald, M. L., Ohyagi, Y., Younkin, S. G., Bu, G.*, and Kanekiyo, T*. ABCA7 Deficiency Accelerates Amyloid-beta Generation and Alzheimer's Neuronal Pathology. The Journal of neuroscience : the official journal of the Society for Neuroscience 36, 3848-3859, 2016.

Zhang, Y. J., Gendron, T. F., Grima, J. C., Sasaguri, H., Jansen-West, K., Xu, Y. F., Katzman, R. B., Gass, J., Murray, M. E., Shinohara, M., Lin, W. L., Garrett, A., Stankowski, J. N., Daughrity, L., Tong, J., Perkerson, E. A., Yue, M., Chew, J., Castanedes-Casey, M., Kurti, A., Wang, Z. S., Liesinger, A. M., Baker, J. D., Jiang, J., Lagier-Tourenne, C., Edbauer, D., Cleveland, D. W., Rademakers, R., Boylan, K. B., Bu, G., Link, C. D., Dickey, C. A., Rothstein, J. D., Dickson, D. W., Fryer, J. D., and Petrucelli, L*. C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins. Nature neuroscience 19, 668-677, 2016.

Fu, Y., Zhao, J., Atagi, Y., Nielsen, H. M., Liu, C. C., Zheng, H., Shinohara, M., Kanekiyo, T., and Bu, G. Apolipoprotein E lipoprotein particles inhibit amyloid-beta uptake through cell surface heparan sulphate proteoglycan. Molecular neurodegeneration 11, 37, 2016.

Takasugi, N., Sasaki, T., Shinohara, M., Iwatsubo, T., and Tomita, T. Synthetic ceramide analogues increase amyloid-beta 42 production by modulating gamma-secretase activity. Biochemical and biophysical research communications 457, 194-199, 2015.

Cook, C., Kang, S. S., Carlomagno, Y., Lin, W. L., Yue, M., Kurti, A., Shinohara, M., Jansen-West, K., Perkerson, E., Castanedes-Casey, M., Rousseau, L., Phillips, V., Bu, G., Dickson, D. W., Petrucelli, L., and Fryer, J. D. Tau deposition drives neuropathological, inflammatory and behavioral abnormalities independently of neuronal loss in a novel mouse model. Human molecular genetics 24, 6198-6212, 2015.

Casey, C. S., Atagi, Y., Yamazaki, Y., Shinohara, M., Tachibana, M., Fu, Y., Bu, G., and Kanekiyo, T. Apolipoprotein E Inhibits Cerebrovascular Pericyte Mobility through a RhoA Protein-mediated Pathway. The Journal of biological chemistry 290, 14208-14217, 2015.

Shinohara, M., Fujioka, S., Murray, M. E., Wojtas, A., Baker, M., Rovelet-Lecrux, A., Rademakers, R., Das, P., Parisi, J. E., Graff-Radford, N. R., Petersen, R. C., Dickson, D. W., and Bu, G. Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer's disease. Brain : a journal of neurology 137, 1533-1549, 2014.

Zhao, J., Fu, Y., Liu, C. C., Shinohara, M., Nielsen, H. M., Dong, Q., Kanekiyo, T., and Bu, G. Retinoic acid isomers facilitate apolipoprotein E production and lipidation in astrocytes through the retinoid X receptor/retinoic acid receptor pathway. The Journal of biological chemistry 289, 11282-11292, 2014.

Shinohara, M., Petersen, R. C., Dickson, D. W., and Bu, G. Brain regional correlation of amyloid-beta with synapses and apolipoprotein E in non-demented individuals: potential mechanisms underlying regional vulnerability to amyloid-beta accumulation. Acta neuropathologica 125, 535-547, 2013.

Li, J., Kanekiyo, T., Shinohara, M., Zhang, Y., LaDu, M. J., Xu, H., and Bu, G. Differential regulation of amyloid-beta endocytic trafficking and lysosomal degradation by apolipoprotein E isoforms. The Journal of biological chemistry 3, 187-189, 2013.

Kanekiyo, T., Cirrito, J. R., Liu, C. C., Shinohara, M., Li, J., Schuler, D. R., Shinohara, M., Holtzman, D. M., and Bu, G. Neuronal clearance of amyloid-beta by endocytic receptor LRP1. The Journal of neuroscience : the official journal of the Society for Neuroscience 33, 19276-19283, 2013.

Takeda,S., Sato, N.*, Ikimura, K, Nishino, H., Rakugi, H., Morishita R*. Increased Blood-Brain Barrier Vulnerability to Systemic Inflammation in Alzheimer Disease Mouse Model. Neurobiology of Aging, 34(8), 2064-70, 2013.

Shimamura, M., Sato, N., Nakagami, H., Osako, M.K., Kyutoku, M., Wakayama, K., Morishita, R. Chronic deposition of Aβ influences microcirculation in the chronic stage of cerebral Ischemia. Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry, 13(1), 77-80, 2013.

Kanekiyo, T., Liu, C. C., Shinohara, M., Li, J., and Bu, G. LRP1 in brain vascular smooth muscle cells mediates local clearance of Alzheimer's amyloid-beta. The Journal of neuroscience : the official journal of the Society for Neuroscience 32, 16458-16465, 2012.

Sato, N.*, Okochi, M., Shinohara, M., Thinakaran, G., Takeda, S., Fukumori, A., Shinohara-Noma, M., Mori-Ueda, M., Hamada, H., Takeda, M., Rakugi, H., Morishita, R. Differential Regulation of Amyloid Precursor Protein /Presenilin 1 Interaction during Aβ40/42 Production Detected Using Fusion Constructs. PLoS ONE 7(11), e48551, 2012.

Takeda, S., Sato, N.*, Uchio-Yamada, K., Yu, H., Moriguchi, A., Rakugi, H., Morishita, R. Oral Glucose Loading Modulates Plasma Aβ Level in Alzheimer Disease Patients: Potential Diagnostic Method for Alzheimer Disease. Dementia and Geriatric Cognitive Disorders, 34(1), 25-30, 2012.

Hayashi H, Nakagami H, Takeichi M, Shimamura M, Koibuchi N, Oiki E, Sato N, Koriyama H, Mori M, Gerardo Araujo R, Maeda A, Morishita R, Tamai K, Kaneda Y*. HIG1, a novel regulator of mitochondrial γ-secretase, maintains normal mitochondrial function. FASEB J. 26(6), 2306-17, 2012.

Shimamura M, Taniyama Y, Katsuragi N, Koibuchi N, Kyutoku M, Sato N, Allahtavakoli M, Wakayama K, Nakagami H, and Morishita R*. Role of Central Nervous System Periostin in Cerebral Ischemia. Stroke, 43(4), 1108-14, 2012.

Takeda, S., Sato, N.*, Ikimura, K., Nishino, H., Rakugi, R., Morishita, R*. Novel microdialysis method to assess neuropeptides and large molecules in free-moving mouse. Neuroscience, 186, 110-9, 2011.

Shinohara, M, Sato, N, Kurinami, H., Takeuchi, D., Takeda, S, Shimamura, M., Yamashita, T., Uchiyama, Y., Rakugi, H., Morishita, R*. Reduction of brain Aβ by fluvastatin, an HMG-CoA reductase inhibitor, through increase in degradation of APP-CTFs and Aβ clearance. The Journal of Biological Chemistry 285, 22091-22102, 2010.

Takeda, S., Sato, N., Uchio-Yamada, K, Sawada, K., Kunieda, T., Takeuchi, D., Kurinami, H., Shinohara, M., Rakugi, H., Morishita, R*. Diabetes accelerated memory dysfunction via cerebrovascular inflammation and Aβ deposition in an Alzheimer mouse model with diabetes. Proc Natl Acad Sci U S A, 13, 107, 7036-41, 2010.

Takeda, S., Sato, N., Takeuchi, D., Kurinami, H., Shinohara, M., Niisato, K., Kano, M., Ogihara, T., Rakugi, H., Morishita, R*. Angiotensin Receptor Blocker Prevented β-Amyloid-Induced Cognitive Impairment Associated with Recovery of Neurovascular Coupling. Hypertension, 54, 1345-52, 2009.

Hayashi S*, Sato N, Yamamoto A, Ikegame Y, Nakashima S, Ogihara T, Morishita R. Alzheimer disease-associated peptide, amyloid beta40, inhibits vascular regeneration with induction of endothelial autophagy. Arterioscler Thromb Vasc Biol. 29, 1909-15, 2009.

Takeda, S., Sato, N., Niisato, K., Takeuchi, D., Kurinami, H., Shinohara, M., Rakugi, H., Kano, M., Morishita, R*. Validation of Aβ1-40 Administration into Mouse Cerebroventricles as an Animal Model for Alzheimer Disease. Brain Research, 1280, pp137-147, 2009

Takeda, S., Sato, N., Uchio-Yamada, K., Sawada, K., Kunieda, T., Takeuchi, D., Kurinami, H., Shinohara, M., Rakugi, H., Morishita, R*. Elevation of Plasma β-amyloid Level by Glucose Loading in Alzheimer Mouse Models. Biochemical and Biophysical Research Communications, 385, 193-197, 2009.

Wakayama K, Shimamura M, Sata M, Koibuchi N, Sato N, Ogihara T, Morishita R*. A model of cerebrovascular injury in rats. . 175, 187-95, 2008.

Kurinami H, Sato N, Shinohara M, Takeuchi D, Takeda S, Shimamura M, Ogihara T and Morishita R*.. Prevention of amyloid β-induced memory impairment by fluvastatin, associated with the decrease in amyloid β accumulation and oxidative stress in amyloid βinjection mouse model. International Journal of Molecular Medicine 21, 531-7, 2008.

Takeuchi D, Sato N, Shimamura M, Kurinami H, Takeda S , Shinohara M , Suzuki S , Kojima M, Ogihara T and Morishita R*. Alleviation of Aβ-induced cognitive impairment by ultrasound-mediated gene transfer of HGF in a mouse model. Gene Therapy, 15, 561-71, 2008.

Hayashi H, Nakagami H*, Takami Y, Sato N, Saitoh Y, Nishikawa T, Mori M, Koriyama H, Tamai K, Morishita R, Kaneda Y*. Involvement of gamma-secretase in postnatal angiogenesis. Biochem. Biophys. Res. Commun. 363, 584-90, 2007.

Shimamura M, Sato N, Sata, M, Kurinami, H, Takeuchi, D, Wakayama, K, Hayashi, T, Iida, H, Morishita R*. Delayed Post-ischemic Treatment with Fluvastatin Improved Learning and Memory Deficit After Stroke in Rats. Stroke 38, 3251-8, 2007.

Shimamura M, Sato N, Sata M, Wakayama K, Ogihara T, Morishita R*. Expression of hepatocyte growth factor and c-Met after spinal cord injury in rats. Brain Res. 1151, 188-94, 2007.

Wakayama K, Shimamura M, Sata M, Sato N, Kawakami K, Fukuda H, Tomimatsu T, Ogihara T, Morishita R*. Quantitative measurement of neurological deficit after mild (30 min) transient middle cerebral artery occlusion in rats. Brain Res. 1130, 181-7, 2007.

Shimamura M, Sato N, Waguri S, Uchiyama Y, Hayashi T, Iida H, Nakamura T, Ogihara T, Kaneda Y, Morishita R*. Gene Transfer of Hepatocyte Growth Factor Gene Improves Learning and Memory in the Chronic Stage of Cerebral Infarction. Hypertension. 47, 742-51, 2006.

Sato N, Okochi M, Taniyama Y, Kurinami H, Shimamura M, Takeuchi D, Hamada H, Fukumori A, Kiyosue K, Taguchi T, Tanaka T, Miyasaka M, Takeda M, Ogihara T, Morishita R*. Development of new screening system for Alzheimer Disease, in vitro Aβ sink assay, to identify the dissociation of soluble Aβ from fibrils. Neuobiology of Disease 22, 487-495, 2006.

Shimamura, M., Sato, N, Taniyama, Y., Kurinami, H., Tanaka, H., Takami, T., Ogihara, T., Tohyama, M., Kaneda, Y. & Morishita, R*. Gene transfer into adult rat spinal cord using naked plasmid DNA and ultrasound microbubbles. J. Gene Med. 7, 1468-74, 2005.

Shimamura M, Sato N, Taniyama Y, Yamamoto S, Endoh M, Kurinami H, Aoki M, Ogihara T, Kaneda Y, Morishita R*. Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound. Gene Ther. 11,1532-9, 2004.

Shimamura M, Sato N, Oshima K, Aoki M, Kurinami H, Waguri S, Uchiyama Y, Ogihara T, Kaneda Y, Morishita R*. A novel therapeutic strategy to treat brain ischemia: Over-expression of hepatocyte growth factor gene reduced ischemic injury without cerebral edema in rat model. Circulation, 109,424-31, 2004.

Suzuki T, Fukuo K*, Suhara T, Yasuda O, Sato N, Takemura Y, Tsubakimoto M, Ogihara T. Eicosapentaenoic acid protects endothelial cells against anoikis through restoration of cFLIP. Hypertension. 42, 342-8, 2003.

Fukuo K*, Yang J, Suzuki T, Kaimoto T, Takemura Y, Yasuda O, Suhara T, Sato N, Ogihara T. Nifedipine upregulates manganese superoxide dismutase expression in vascular smooth muscle cells via endothelial cell-dependent pathways. Hypertens Res. 26, 503-8, 2003.

Fukuo K*, Yang J, Yasuda O, Mogi M, Suhara T, Sato N, Suzuki T, Morimoto S, Ogihara T. Nifedipine Indirectly Upregulates Superoxide Dismutase Expression in Endothelial Cells via Vascular Smooth Muscle Cell–Dependent Pathways. Circulation. 106, 356-61, 2002.

Fukuo K*, Yang J, Yasuda O, Mogi M, Suhara T, Sato N, Suzuki T, Morimoto S, Ogihara T. Nifedipine Indirectly Upregulates Superoxide Dismutase Expression in Endothelial Cells via Vascular Smooth Muscle Cell–Dependent Pathways. Circulation. 106, 356-61, 2002.

Mori M, Nakagami H, Morishita R, Mitsuda N, Yamamoto K, Yoshimura S, Ohkubo N, Sato N, Ogihara T, Kaneda Y*. N141I mutant presenilin-2 gene enhances neuronal cell death and decreases bcl-2 expression. Life Sci. 70,2567-80, 2002.

Sato N, Urano F, Yoon Leem J, Kim SH, Li M, Donoviel D, Bernstein A, Lee AS, Ron D, Veselits ML, Sisodia SS, Thinakaran G*. Upregulation of BiP and CHOP by the unfolded-protein response is independent of presenilin expression. Nat Cell Biol. 2, 863-70, 2000.

Hatanaka Y, Kamino K, Fukuo K*, Mitsuda N, Nishiwaki-Ueda Y, Sato N, Satoh T, Yamamoto H, Yoneda H, Imagawa M, Miki T, Ohta S, Ogihara T. Low density lipoprotein receptor-related protein gene polymorphisms and risk for late-onset Alzheimer's disease in a Japanese population. Clin Genet. 58,319-23, 2000.

Mitsuda N*, Ohkubo N, Tamatani M, Lee YD, Taniguchi M, Namikawa K, Kiyama H, Yamaguchi A, Sato N, Sakata K, Ogihara T, Vitek MP, Tohyama M. Activated cyclic AMP- response element-binding protein regulates neuronal expression of presenilin-1. J Biol Chem. 276,9688-98, 2001.

Sato N, Kamino K*, Tateishi K, Satoh T, Nishiwaki Y, Yoshiiwa A, Miki T, Ogihara T. Elevated Amyloid β Protein (1-40) Level Induces CREB Phosphorylation  at serine-133 via p44/p42 MAP Kinase(ERK1/2)-dependent Pathway in Rat Pheochromocytoma PC12 Cells. Biochem. Biophys. Res. Commun. 232, 637-642, 1997.

Nishiwaki Y, Kamino K*, Yoshiiwa A, Sato N, Tateishi K, Takeda M, Kobayashi T, Yamamoto H, Nonomura Y, Yoneda H, Sakai T, Imagawa M, Miki T, Ogihara T. T/G polymorphism at intron 9 of presenilin 1 gene is associated with, but not responsible for sporadic late-onset Alzheimer's disease in Japanese population. Neurosci Lett., 227, 123-6, 1997.

Yoshiiwa A, Kamino K*, Yamamoto H, Kobayashi T, Imagawa M,Nonomura Y, Yoneda H, Sakai T, Nishiwaki Y, Sato N,Rakugi H, Miki T, Ogihara T. a1-Antichymotrypsin as a risk modifier for late-onset Alzheimer’s disease in Japanese Apolipoprotein E e4 allele carriers. Annals of Neurology, 42, 115-117, 1997.

Sato N, Fujio Y*, Yamada-Honda Y, Funai H, Wada A, Kawashima S, Awata N, Shibata N. Elevated calcium level induces calcium-dependent proteolysis of A-CAM (N-cadherin) in heart - analysis by detergent-treated model. Biochem. Biophys. Res. Commun.，217, 649-653, 1995.

Fujio Y*, Yamada-Honda Y, Sato N, Funai H, Wada A, Awata N, Shibata N. Disruption of cell-cell adhesion in an inbred strain of hereditary cardiomyopathic hamster (Bio 14.6). Cardiovascular Research, 30, 899-904, 1995.

Review etc.:

Zonghua Li, Francis Shue, Na Zhao, Shinohara M, Guojun Bu
APOE2: protective mechanism and therapeutic implications for Alzheimer’s disease
Molecular Neurodegeneration volume 15, Article number: 63 (2020)

Sato N
Emerging role of the apolipoproteins APOE and APOJ in the interaction between diabetes and Alzheimer’s disease
The Journal of Clinical Endocrinology & Metabolism, dgaa570, 07 Sep. 2020, doi.org/10.1210/clinem/dgaa570

Shinohara M, Sato N. Bidirectional interactions between diabetes and Alzheimer's disease.Neurochem Int.2017 Sep;108:296-302.doi: 10.1016/j.neuint.2017.04.020

Shinohara M, Tachibana M., Kanekiyo, T, Bu, G. Role of LRP1 in the pathogenesis of Alzheimer's disease: evidence from clinical and preclinical studies. J. Lipid Res. 58(7):1267:1281,2017. doi: 10.1194/jlr.R075796

Sato, N.*, Morishita, R. The Roles of Lipid and Glucose Metabolism in Modulation of b-Amyloid, Tau, and Neurodegeneration in the Pathogenesis of Alzheimer disease. Front. Aging Neurosci. | doi: 10.3389/fnagi.2015.00199, 2015.

Sato, N.*, Morishita, R. Brain alterations and clinical symptoms of dementia in diabetes: Aβ/tau-dependent and independent mechanisms. Frontiers in Endocrinology. Front. Endocrinol. | doi: 10.3389/fendo.2014.00143, 2014.

Takeda, S., Sato, N.*, Morishita, R.* Systemic inflammation, blood-brain barrier vulnerability and cognitive / non-cognitive symptoms in Alzheimer disease: Relevance to pathogenesis and therapy. Front. Aging Neurosci. doi: 10.3389/fnagi.2014.00171, 2014.

Shinohara, M., Sato, N.*, Kurinami, H., Shimamura, M., Hamasaki, T., Chatterjee, A., Rakugi, H., Morishita, R. Possible modification of Alzheimer's disease by statins in midlife: interactions with genetic and non-genetic risk factors. Front. Aging Neurosci. doi: 10.3389/fnagi.2014.00071, 2014

Sato N* and Morishita R*. Roles of Vascular and Metabolic Components in Cognitive Dysfunction of Alzheimer disease: Short- and Long-term Modification by Non-genetic Risk Factors. Front. Aging Neurosci. 5:64. doi: 10.3389/fnagi.2013.00064, 2013.

Shinohara, M.*, Bu, G. What can we learn from regional vulnerability to Aβ accumulation in non-demented individuals? Neurodegenerative disease management, 3(3), 187-189, 2013.

Sato, N.*, Morishita, R.* Plasma Abeta: A Possible Missing Link Between Alzheimer Disease and Diabetes. Diabetes, 62, 1005-1006, 2013.

Kurnami H, Shimamura M, Sato N, Nakagami H, Morishita R*. Do angiotensin receptor blockers protect against Alzheimer's disease? Drugs&Aging.  30,367-72, 2013. 

Sato, N.*, Shinohara, M., Rakugi, H., Morishita, R. Dual effects of statins on Abeta metabolism: Up-regulation of degradation of APP-CTF and Abeta clearance. Neurodegenerative diseases, 10(1-4),305-8, 2012.

Shimamura M, Sato N, Nakagami H, Taniyama Y, Morishita R*. Development of nucleic acid drugs for neurological disorders. Curr Top Med Chem. 12(15),1621-9, 2012. 

Shimamura M, Sato N, Morishita R*. Experimental and clinical application of plasmid DNA in the field of central nervous diseases. Curr Gene Ther., 11(6), 491-500, 2011.

Takeda S, Sato N*, Rakugi H, Morishita R*. Molecular mechanisms linking diabetes mellitus and Alzheimer disease: beta-amyloid peptide, insulin signaling, and neuronal function. Mol Biosyst. 7(6),1822-7, 2011.

Sato, N.*, Takeda, S., Uchio-Yamada, K., Ueda, H., Fujisawa, T., Rakugi, H., Morishita, R. Role of insulin signaling in the interaction between Alzheimer disease and diabetes mellitus: a missing link to therapeutic potential. Current Aging Science, 4, 118-127, 2011.

Takeda, S., Sato, N., Rakugi, H., Morishita, R*. Plasma Beta-Amyloid as Potential Biomarker of Alzheimer Disease: Possibility of Diagnostic Tool of Alzheimer Disease. Molecular BioSystems, 6, 1760-1766, 2010.

Fournier A*, Oprisiu-Fournier R, Serot JM, Godefroy O, Achard JM, Faure S, Mazouz H, Temmar M, Albu A, Bordet R, Hanon O, Gueyffier F, Wang J, Black S, Sato N. Prevention of dementia by antihypertensive drugs: how AT1-receptor-blockers and dihydropyridines better prevent dementia in hypertensive patients than thiazides and ACE-inhibitors. Expert Rev Neurother. 9(9),1413-31, 2009.

Takeda S, Sato N, Ogihara T, Morishita R*. The Renin-Angiotensin System, Hypertension and cognitive dysfunction in Alzheimer's Disease: New Therapeutic Potential. Frontiers in Bioscience. , 2008.

Sato N, Shimamura M, Takeuchi D, Kurinami H, Ogihara T, Morishita R*. Gene Therapy for Ischemic Brain Disease with special reference to Vascular Dementia. Geriatrics and Gerontology International. 2006.

Shimamura, M., Sato, N, Yoshimura S, Kaneda, Y., Morishita, R*. HVJ-based non-viral gene transfer method: successful gene therapy using HGF and VEGF genes in experimental ischemia Frontiers in Bioscience. 11, 753-759, 2006.

Sato N, Shimamura M, Morishita R*. Recent Progress in Cerebrovascular Gene Therapy. Current Neurovascular Research. 2, 235-247, 2005.

Thinakaran G*, Bowen JW, Ito D, Leem JY, Veselits ML, Sato N. Investigation of unfolded-protein response in cells expressing familial Alzheimer's disease-linked presenilin variants. Methods Mol Biol. 232, 203-16, 2003.

Miki T*, Nakura J, Ye L, Mitsuda N, Morishima A, Sato N, Kamino K, Ogihara T. Molecular and epidemiological studies of Werner syndrome in the Japanese population. Mech Ageing Dev. 98, 255-65, 1997.

Book:

Shinohara M, Sato N.
The Roles of Apolipoprotein E, Lipids, and Glucose in the Pathogenesis of Alzheimer’s Disease.
Diabetes Mellitus, A risk factor for Alzheimer's Disease. Eds: Yusaku Nakabeppu & Toshiharu Ninomiya. Springer Nature Singapore Pte Ltd. 85-101, 2019.

Sato, N., Morishita, R. Aβ Deposition, Insulin Signaling, and Tau Phosphorylation in Animal Models of Alzheimer Disease and Diabetes. Metabolic Syndrome and Neurological Disorders. Eds: Akhlaq A. Farooqui, Tahira Farooqui. John Wiley & Sons, Inc.383-394, 2013.

Takeda, S., Sato, N., Rakugi, H., Morishita, R*. Animal Models of Alzheimer Disease for Translational Research: Current and Future Concepts. Horizons in Neuroscience Research. Volume 4 (Hardcover), Nova Science Publishers, Inc. 2010.

Sato, N., Thinakaran, G*. The Unfolded Protein Response-mediated Upregulation of BiP and CHOP Is not Affected by Presenilin Expression. Alzheimer's Disease: Advances in Etiology, Pathogenesis and Therapeutics. Eds: Khalid Iqbal, Sangram S. Sisodia and Bengt Winblad. John Wiley & Sons Ltd. 559-568, 2001.

Kamino K*, Yoshiiwa A, Nishiwaki Y, Sato N, Tateishi K, Kudo T, Nishimura T, Takeda M, Miki T and Ogihara T. Integration of genetic factors into pathogenesis of Alzheimer's disease.
Research and Practice in Alzheimer's disease. Eds: Vellas B. et al. Springer Publishing Company, Paris. 51-70, 1998.

Sato N, Kamino K*, Tateishi K, Satoh T, Nishiwaki Y, Yoshiiwa A, Miki T, Ogihara T. Differential effects on CREB Phosphorylation at serine-133 between Amyloid beta Protein(1-40) and Amyloid beta Protein(1-42) at the concentrations of μM. Ed: Yakura, H. Kinases and Phosphatases in Lymphocyte and Neuronal Signaling, 301-302, 1997.

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