nach oben

Erschienen in:

28.05.2019 | Original Communication

In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer’s disease

verfasst von: Tatsuhiro Terada, Masamichi Yokokura, Tomokazu Obi, Tomoyasu Bunai, Etsuji Yoshikawa, Ichiro Ando, Hitoshi Shimada, Tetsuya Suhara, Makoto Higuchi, Yasuomi Ouchi

Erschienen in: Journal of Neurology | Ausgabe 9/2019

Einloggen, um Zugang zu erhalten

Abstract

Objective

Neuronal damage and neuroinflammation are important events occurring in the brain of Alzheimer’s disease (AD). The purpose of this study was to clarify in vivo mutual relationships among abnormal tau deposition, neuroinflammation and cognitive impairment in patients with early AD using positron emission tomography (PET) with [¹¹C]PBB3 and [¹¹C]DPA713.

Methods

Twenty patients with early AD and 20 age-matched normal control (NC) subjects underwent a series of PET measurements with [¹¹C]PBB3 for tau aggregation and [¹¹C]DPA713 for microglial activation (neuroinflammation). Inter- and intrasubject comparisons were performed regarding the levels of [¹¹C]PBB3 binding potential (BP_ND) and [¹¹C]DPA713 BP_ND in the light of cognitive functions using statistical parametric mapping (SPM) and regions of interest (ROIs) method.

Results

The [¹¹C]PBB3 BP_ND was greater in the temporo-parietal regions of AD patents than NC subjects, and a similar increasing pattern of [¹¹C]DPA713 BP_ND was observed in the same patients. Correlation analyses within the AD group showed a positive direct correlation between [¹¹C]PBB3 BP_ND and [¹¹C]DPA713 BP_ND in the parahippocampus. Pass analysis revealed that cognitive impairment was more likely linked to the level of the parahippocampal [¹¹C]PBB3 BP_ND than that of [¹¹C]DPA713 BP_ND.

Conclusions

The pattern of abnormal tau deposition was very similar to that of neuroinflammation in patients with early-stage AD. Specifically, the direct positive correlation of tau pathology with neuroinflammation in the parahippocampus suggests that neuronal damage in this region is closely associated with microglial activation. Consistently, tau aggregation in this region matters more than neuroinflammation regarding the cognitive deterioration in AD.

Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH (2011) 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. Alzheimer’s Dementia J Alzheimer’s Assoc 7:270–279CrossRef

Annicchiarico R, Federici A, Pettenati C, Caltagirone C (2007) Rivastigmine in Alzheimer’s disease: cognitive function and quality of life. Ther Clin Risk Manag 3:1113–1123PubMedPubMedCentral

Asai H, Ikezu S, Tsunoda S, Medalla M, Luebke J, Haydar T, Wolozin B, Butovsky O, Kugler S, Ikezu T (2015) Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat Neurosci 18:1584–1593CrossRefPubMedPubMedCentral

Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259CrossRefPubMed

Braak H, Del Tredici K (2012) Alzheimer’s disease: pathogenesis and prevention. Alzheimer’s Dementia J Alzheimer’s Assoc 8:227–233CrossRef

Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, Jones T, Banati RB (2001) In-vivo measurement of activated microglia in dementia. Lancet 358:461–467CrossRefPubMed

Carlson JO, Gatz M, Pedersen NL, Graff C, Nennesmo I, Lindstrom AK, Gerritsen L (2015) Antemortem prediction of braak stage. J Neuropathol Exp Neurol 74:1061–1070CrossRefPubMed

Cerami C, Iaccarino L, Perani D (2017) Molecular imaging of neuroinflammation in neurodegenerative dementias: the role of in vivo PET imaging. Int J Mol Sci 18:993CrossRefPubMedCentral

Chiotis K, Stenkrona P, Almkvist O, Stepanov V, Ferreira D, Arakawa R, Takano A, Westman E, Varrone A, Okamura N, Shimada H, Higuchi M, Halldin C, Nordberg A (2018) Dual tracer tau PET imaging reveals different molecular targets for (11)C-THK5351 and (11)C-PBB3 in the Alzheimer brain. Eur J Nucl Med Mol Imag 45:1605–1617CrossRef

10.

Doorduin J, Klein HC, Dierckx RA, James M, Kassiou M, de Vries EF (2009) [11C]-DPA-713 and [18F]-DPA-714 as new PET tracers for TSPO: a comparison with [11C]-(R)-PK11195 in a rat model of herpes encephalitis. Mol Imag Biol 11:386–398CrossRef

11.

Guggenberger R, Fischer DR, Metzler P, Andreisek G, Nanz D, Jacobsen C, Schmid DT (2013) Bisphosphonate-induced osteonecrosis of the jaw: comparison of disease extent on contrast-enhanced MR imaging, [18F] fluoride PET/CT, and conebeam CT imaging. AJNR Am J Neuroradiol 34:1242–1247CrossRefPubMedPubMedCentral

12.

Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185CrossRefPubMed

13.

Jefferies WA, Food MR, Gabathuler R, Rothenberger S, Yamada T, Yasuhara O, McGeer PL (1996) Reactive microglia specifically associated with amyloid plaques in Alzheimer’s disease brain tissue express melanotransferrin. Brain Res 712:122–126CrossRefPubMed

14.

Kimura Y, Endo H, Ichise M, Shimada H, Seki C, Ikoma Y, Shinotoh H, Yamada M, Higuchi M, Zhang MR, Suhara T (2016) A new method to quantify tau pathologies with (11)C-PBB3 PET using reference tissue voxels extracted from brain cortical gray matter. EJNMMI Res 6:24CrossRefPubMedPubMedCentral

15.

Kimura Y, Ichise M, Ito H, Shimada H, Ikoma Y, Seki C, Takano H, Kitamura S, Shinotoh H, Kawamura K, Zhang MR, Sahara N, Suhara T, Higuchi M (2015) PET quantification of tau pathology in human brain with 11C-PBB3. J Nucl Med 56:1359–1365CrossRefPubMed

16.

Li Y, Tan MS, Jiang T, Tan L (2014) Microglia in Alzheimer’s disease. Biomed Res Int 2014:437483PubMedPubMedCentral

17.

JrK Mai, Assheuer J, Paxinos G (1997) Atlas of the human brain. Academic Press, San Diego

18.

Maphis N, Xu G, Kokiko-Cochran ON, Jiang S, Cardona A, Ransohoff RM, Lamb BT, Bhaskar K (2015) Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain 138:1738–1755CrossRefPubMedPubMedCentral

19.

Maruyama M, Shimada H, Suhara T, Shinotoh H, Ji B, Maeda J, Zhang MR, Trojanowski JQ, Lee VM, Ono M, Masamoto K, Takano H, Sahara N, Iwata N, Okamura N, Furumoto S, Kudo Y, Chang Q, Saido TC, Takashima A, Lewis J, Jang MK, Aoki I, Ito H, Higuchi M (2013) Imaging of tau pathology in a tauopathy mouse model and in Alzheimer patients compared to normal controls. Neuron 79:1094–1108CrossRefPubMed

20.

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) 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. Alzheimer’s Dementia J Alzheimer’s Assoc 7:263–269CrossRef

21.

Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, Rhodes C, Pulford DJ, Bennacef I, Parker CA, StJean PL, Cardon LR, Mooser VE, Matthews PM, Rabiner EA, Rubio JP (2012) An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab 32:1–5CrossRefPubMed

22.

Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapere JJ, Lindemann P, Norenberg MD, Nutt D, Weizman A, Zhang MR, Gavish M (2006) Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci 27:402–409CrossRefPubMed

23.

Passamonti L, Vazquez Rodriguez P, Hong YT, Allinson KS, Williamson D, Borchert RJ, Sami S, Cope TE, Bevan-Jones WR, Jones PS, Arnold R, Surendranathan A, Mak E, Su L, Fryer TD, Aigbirhio FI, O’Brien JT, Rowe JB (2017) 18F-AV-1451 positron emission tomography in Alzheimer’s disease and progressive supranuclear palsy. Brain 140:781–791PubMedPubMedCentral

24.

Pontecorvo MJ, Devous MD Sr, Navitsky M, Lu M, Salloway S, Schaerf FW, Jennings D, Arora AK, McGeehan A, Lim NC, Xiong H, Joshi AD, Siderowf A, Mintun MA (2017) Relationships between flortaucipir PET tau binding and amyloid burden, clinical diagnosis, age and cognition. Brain 140:748–763PubMedPubMedCentral

25.

Saint-Aubert L, Lemoine L, Chiotis K, Leuzy A, Rodriguez-Vieitez E, Nordberg A (2017) Tau PET imaging: present and future directions. Mol Neurodegener 12:19CrossRefPubMedPubMedCentral

26.

Sarlus H, Heneka MT (2017) Microglia in Alzheimer’s disease. J Clin Invest 127:3240–3249CrossRefPubMedPubMedCentral

27.

Scholl M, Lockhart SN, Schonhaut DR, O’Neil JP, Janabi M, Ossenkoppele R, Baker SL, Vogel JW, Faria J, Schwimmer HD, Rabinovici GD, Jagust WJ (2016) PET imaging of Tau deposition in the aging human brain. Neuron 89:971–982CrossRefPubMedPubMedCentral

28.

Schonheit B, Zarski R, Ohm TG (2004) Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology. Neurobiol Aging 25:697–711CrossRefPubMed

29.

Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT (2011) Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med 1:a006189CrossRefPubMedPubMedCentral

30.

Shimada H, Kitamura S, Shinotoh H, Endo H, Niwa F, Hirano S, Kimura Y, Zhang MR, Kuwabara S, Suhara T, Higuchi M (2017) Association between Abeta and tau accumulations and their influence on clinical features in aging and Alzheimer’s disease spectrum brains: a [11C]PBB3-PET study. Alzheimers Dement (Amst) 6:11–20

31.

Spangenberg EE, Lee RJ, Najafi AR, Rice RA, Elmore MR, Blurton-Jones M, West BL, Green KN (2016) Eliminating microglia in Alzheimer’s mice prevents neuronal loss without modulating amyloid-beta pathology. Brain 139:1265–1281CrossRefPubMedPubMedCentral

32.

Stage FKCH, Nora A (2004) Path analysis: an introduction and analysis of a decade of research. J Educ Res 98:5–13CrossRef

33.

Terada T, Yokokura M, Yoshikawa E, Futatsubashi M, Kono S, Konishi T, Miyajima H, Hashizume T, Ouchi Y (2016) Extrastriatal spreading of microglial activation in Parkinson’s disease: a positron emission tomography study. Ann Nucl Med 30:579–587CrossRefPubMed

34.

Tombaugh TN, McIntyre NJ (1992) The mini-mental state examination: a comprehensive review. J Am Geriatr Soc 40:922–935CrossRefPubMed

35.

Trojanowski JQ, Lee VM (2000) “Fatal attractions” of proteins. A comprehensive hypothetical mechanism underlying Alzheimer’s disease and other neurodegenerative disorders. Ann N Y Acad Sci 924:62–67CrossRefPubMed

36.

Tronel C, Largeau B, Santiago Ribeiro MJ, Guilloteau D, Dupont AC, Arlicot N (2017) Molecular targets for PET imaging of activated microglia: the current situation and future expectations. Int J Mol Sci 18:802CrossRefPubMedCentral

37.

Yokokura M, Mori N, Yagi S, Yoshikawa E, Kikuchi M, Yoshihara Y, Wakuda T, Sugihara G, Takebayashi K, Suda S, Iwata Y, Ueki T, Tsuchiya KJ, Suzuki K, Nakamura K, Ouchi Y (2011) In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nuclear Med Mol Imaging 38:343–351CrossRef

38.

Yokokura M, Terada T, Bunai T, Nakaizumi K, Takebayashi K, Iwata Y, Yoshikawa E, Futatsubashi M, Suzuki K, Mori N, Ouchi Y (2017) Depiction of microglial activation in aging and dementia: positron emission tomography with [11C]DPA713 versus [11C](R)PK11195. J Cereb Blood Flow Metab 37:877–889CrossRefPubMed

39.

Zhang F, Jiang L (2015) Neuroinflammation in Alzheimer’s disease. Neuropsychiatr Dis Treat 11:243–256CrossRefPubMedPubMedCentral

Titel: In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer’s disease
verfasst von: Tatsuhiro Terada
Masamichi Yokokura
Tomokazu Obi
Tomoyasu Bunai
Etsuji Yoshikawa
Ichiro Ando
Hitoshi Shimada
Tetsuya Suhara
Makoto Higuchi
Yasuomi Ouchi
Publikationsdatum: 28.05.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Neurology / Ausgabe 9/2019
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI: https://doi.org/10.1007/s00415-019-09400-2

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

25.04.2024 | Hypotonie | Nachrichten

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer’s disease

Abstract

Objective

Methods

Results

Conclusions

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Neurologie

Springer Medizin

Abstract

Objective

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 9/2019

HSV-2-encephalitis in a patient with multiple sclerosis treated with ocrelizumab

Neuronal spiking in the pedunculopontine nucleus in progressive supranuclear palsy and in idiopathic Parkinson’s disease

Comparison of high-frequency and ultrahigh-frequency probes in chronic inflammatory demyelinating polyneuropathy

Stroke severity in patients with preceding direct oral anticoagulant therapy as compared to vitamin K antagonists

Analytical and clinical performances of the automated Lumipulse cerebrospinal fluid Aβ42 and T-Tau assays for Alzheimer’s disease diagnosis

The Swiss Narcolepsy Scale (SNS) and its short form (sSNS) for the discrimination of narcolepsy in patients with hypersomnolence: a cohort study based on the Bern Sleep–Wake Database

Leitlinien kompakt für die Neurologie

Neu im Fachgebiet Neurologie

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Demenzkranke durch Antipsychotika vielfach gefährdet

Parkinson-Therapie im Wandel – aktuelle Leitlinie im Fokus

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

Update Neurologie