Individual regional associations between Aβ-, tau- and neurodegeneration (ATN) with microglial activation in patients with primary and secondary tauopathies.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
26 Jul 2023
26 Jul 2023
Historique:
received:
22
11
2022
accepted:
10
07
2023
revised:
27
06
2023
medline:
27
7
2023
pubmed:
27
7
2023
entrez:
26
7
2023
Statut:
aheadofprint
Résumé
β-amyloid (Aβ) and tau aggregation as well as neuronal injury and atrophy (ATN) are the major hallmarks of Alzheimer's disease (AD), and biomarkers for these hallmarks have been linked to neuroinflammation. However, the detailed regional associations of these biomarkers with microglial activation in individual patients remain to be elucidated. We investigated a cohort of 55 patients with AD and primary tauopathies and 10 healthy controls that underwent TSPO-, Aβ-, tau-, and perfusion-surrogate-PET, as well as structural MRI. Z-score deviations for 246 brain regions were calculated and biomarker contributions of Aβ (A), tau (T), perfusion (N1), and gray matter atrophy (N2) to microglial activation (TSPO, I) were calculated for each individual subject. Individual ATN-related microglial activation was correlated with clinical performance and CSF soluble TREM2 (sTREM2) concentrations. In typical and atypical AD, regional tau was stronger and more frequently associated with microglial activation when compared to regional Aβ (AD: β
Identifiants
pubmed: 37495886
doi: 10.1038/s41380-023-02188-8
pii: 10.1038/s41380-023-02188-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : EXC 2145 SyNergy - ID 390857198
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : EXC 2155 - project number 39087428
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : HO2402/18-1
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : FOR-2858 project numbers 403161218, 421887978 and 422188432
Organisme : Alzheimer Forschung Initiative (Alzheimer Forschung Initiative e.V.)
ID : 19063p
Informations de copyright
© 2023. The Author(s).
Références
Ziegler-Graham K, Brookmeyer R, Johnson E, Arrighi HM. Worldwide variation in the doubling time of Alzheimer’s disease incidence rates. Alzheimers Dement. 2008;4:316–23.
pubmed: 18790458
doi: 10.1016/j.jalz.2008.05.2479
Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016;8:595–608.
pubmed: 27025652
pmcid: 4888851
doi: 10.15252/emmm.201606210
Kovacs GG. Invited review: neuropathology of tauopathies: principles and practice. Neuropathol Appl Neurobiol. 2015;41:3–23.
pubmed: 25495175
doi: 10.1111/nan.12208
Palleis C, Brendel M, Finze A, Weidinger E, Botzel K, Danek A, et al. Cortical [(18) F]PI-2620 binding differentiates corticobasal syndrome subtypes. Mov Disord. 2021;36:2104–15.
pubmed: 33951244
doi: 10.1002/mds.28624
Braak H, Braak E. Demonstration of amyloid deposits and neurofibrillary changes in whole brain sections. Brain Pathol. 1991;1:213–6.
pubmed: 1669710
doi: 10.1111/j.1750-3639.1991.tb00661.x
Hyman BT, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Carrillo MC, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimers Dement. 2012;8:1–13.
pubmed: 22265587
pmcid: 3266529
doi: 10.1016/j.jalz.2011.10.007
Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1:a006189.
pubmed: 22229116
pmcid: 3234452
doi: 10.1101/cshperspect.a006189
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010;362:329–44.
pubmed: 20107219
doi: 10.1056/NEJMra0909142
Heneka MT, Carson MJ, Khoury JE, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. The Lancet Neurology. 2015;14:388–405.
pubmed: 25792098
pmcid: 5909703
doi: 10.1016/S1474-4422(15)70016-5
Tan MS, Ji X, Li JQ, Xu W, Wang HF, Tan CC, et al. Longitudinal trajectories of Alzheimer’s ATN biomarkers in elderly persons without dementia. Alzheimers Res Ther. 2020;12:55.
pubmed: 32393375
pmcid: 7216714
doi: 10.1186/s13195-020-00621-6
Hampel H, Cummings J, Blennow K, Gao P, Jack CR Jr., Vergallo A. Developing the ATX(N) classification for use across the Alzheimer disease continuum. Nat Rev Neurol. 2021;17:580–9.
pubmed: 34239130
doi: 10.1038/s41582-021-00520-w
Pascoal TA, Benedet AL, Ashton NJ, Kang MS, Therriault J, Chamoun M, et al. Microglial activation and tau propagate jointly across Braak stages. Nat Med. 2021;27:1592–9.
pubmed: 34446931
doi: 10.1038/s41591-021-01456-w
Ishizawa K, Dickson DW. Microglial activation parallels system degeneration in progressive supranuclear palsy and corticobasal degeneration. J Neuropathol Exp Neurol. 2001;60:647–57.
pubmed: 11398841
doi: 10.1093/jnen/60.6.647
Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol. 2013;12:357–67.
pubmed: 23477989
doi: 10.1016/S1474-4422(13)70044-9
Serrano-Pozo A, Mielke ML, Gomez-Isla T, Betensky RA, Growdon JH, Frosch MP, et al. Reactive glia not only associates with plaques but also parallels tangles in Alzheimer’s disease. Am J Pathol. 2011;179:1373–84.
pubmed: 21777559
pmcid: 3157187
doi: 10.1016/j.ajpath.2011.05.047
Werry EL, Bright FM, Piguet O, Ittner LM, Halliday GM, Hodges JR, et al. Recent developments in TSPO PET imaging as a biomarker of neuroinflammation in neurodegenerative disorders. Int J Mol Sci. 2019;20.
Biechele G, Blume T, Deussing M, Zott B, Shi Y, Xiang X, et al. Pre-therapeutic microglia activation and sex determine therapy effects of chronic immunomodulation. Theranostics. 2021;11:8964–76.
pubmed: 34522221
pmcid: 8419052
doi: 10.7150/thno.64022
Cumming P, Burgher B, Patkar O, Breakspear M, Vasdev N, Thomas P, et al. Sifting through the surfeit of neuroinflammation tracers. J Cereb Blood Flow Metab. 2018;38:204–24.
pubmed: 29256293
doi: 10.1177/0271678X17748786
Stefaniak J, O’Brien J. Imaging of neuroinflammation in dementia: a review. J Neurol Neurosurg Psychiatry. 2016;87:21–8.
pubmed: 26384512
Malpetti M, Passamonti L, Jones PS, Street D, Rittman T, Fryer TD, et al. Neuroinflammation predicts disease progression in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 2021;92:769–75.
pubmed: 33731439
doi: 10.1136/jnnp-2020-325549
Brendel M, Barthel H, van Eimeren T, Marek K, Beyer L, Song M, et al. Assessment of 18F-PI-2620 as a biomarker in progressive supranuclear palsy. JAMA Neurol. 2020;77:1408–19.
pubmed: 33165511
doi: 10.1001/jamaneurol.2020.2526
Palleis C, Sauerbeck J, Beyer L, Harris S, Schmitt J, Morenas-Rodriguez E, et al. In Vivo assessment of neuroinflammation in 4-repeat tauopathies. Mov Disord. 2021;36:883–94.
pubmed: 33245166
doi: 10.1002/mds.28395
Jecmenica Lukic M, Kurz C, Respondek G, Grau-Rivera O, Compta Y, Gelpi E, et al. Copathology in progressive supranuclear palsy: does it matter? Mov Disord. 2020;35:984–93.
pubmed: 32125724
doi: 10.1002/mds.28011
Heneka MT, Kummer MP, Latz E. Innate immune activation in neurodegenerative disease. Nat Rev Immunol. 2014;14:463–77.
pubmed: 24962261
doi: 10.1038/nri3705
Dani M, Wood M, Mizoguchi R, Fan Z, Walker Z, Morgan R, et al. Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease. Brain. 2018;141:2740–54.
pubmed: 30052812
Biel D, Suárez-Calvet M, Hager P, Rubinski A, Dewenter A, Steward A, et al. sTREM2 is associated with amyloidrelated p-tau increases and glucose hypermetabolism in Alzheimer’s disease. EMBO Mol Med. 2023;15:e16987.
pubmed: 36620941
pmcid: 9906389
doi: 10.15252/emmm.202216987
Su L, Surendranathan A, Huang Y, Bevan-Jones WR, Passamonti L, Hong YT, et al. Relationship between tau, neuroinflammation and atrophy in Alzheimer’s disease: The NIMROD study. Inf Fusion. 2021;67:116–24.
doi: 10.1016/j.inffus.2020.10.006
Frigerio I, Boon BDC, Lin CP, Galis-de Graaf Y, Bol J, Preziosa P, et al. Amyloid-beta, p-tau and reactive microglia are pathological correlates of MRI cortical atrophy in Alzheimer’s disease. Brain Commun. 2021;3:fcab281.
pubmed: 34927073
pmcid: 8677327
doi: 10.1093/braincomms/fcab281
Jack CR Jr., Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA research framework: toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14:535–62.
pubmed: 29653606
pmcid: 5958625
doi: 10.1016/j.jalz.2018.02.018
Hoglinger GU, Respondek G, Stamelou M, Kurz C, Josephs KA, Lang AE, et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord. 2017;32:853–64.
pubmed: 28467028
pmcid: 5516529
doi: 10.1002/mds.26987
Armstrong MJ, Litvan I, Lang AE, Bak TH, Bhatia KP, Borroni B, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80:496–503.
pubmed: 23359374
pmcid: 3590050
doi: 10.1212/WNL.0b013e31827f0fd1
Palleis C, Sauerbeck J, Beyer L, Harris S, Schmitt J, Morenas-Rodriguez E, et al. In Vivo Assessment of Neuroinflammation in 4-Repeat Tauopathies. Mov Disord. 2021;36:883–94.
pubmed: 33245166
doi: 10.1002/mds.28395
Rauchmann BS, Brendel M, Franzmeier N, Trappmann L, Zaganjori M, Ersoezlue E, et al. Microglial Activation and Connectivity in Alzheimer Disease and Aging. Ann Neurol. 2022;92:768–81.
pubmed: 36053756
doi: 10.1002/ana.26465
Schmitt J, Palleis C, Sauerbeck J, Unterrainer M, Harris S, Prix C, et al. Dual-Phase beta-Amyloid PET Captures Neuronal Injury and Amyloidosis in Corticobasal Syndrome. Front Aging Neurosci. 2021;13:661284.
pubmed: 34054506
pmcid: 8155727
doi: 10.3389/fnagi.2021.661284
Beyer L, Nitschmann A, Barthel H, van Eimeren T, Unterrainer M, Sauerbeck J, et al. Early-phase [(18)F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury. Eur J Nucl Med Mol Imaging. 2020;47:2911–22.
pubmed: 32318783
pmcid: 7567714
doi: 10.1007/s00259-020-04788-w
Wollenweber FA, Darr S, Muller C, Duering M, Buerger K, Zietemann V, et al. Prevalence of amyloid positron emission tomographic positivity in poststroke mild cognitive impairment. Stroke. 2016;47:2645–8.
pubmed: 27539301
doi: 10.1161/STROKEAHA.116.013778
Song M, Scheifele M, Barthel H, van Eimeren T, Beyer L, Marek K, et al. Feasibility of short imaging protocols for [(18)F]PI-2620 tau-PET in progressive supranuclear palsy. Eur J Nucl Med Mol Imaging. 2021;48:3872–85.
pubmed: 34021393
pmcid: 8484138
doi: 10.1007/s00259-021-05391-3
Volter F, Beyer L, Eckenweber F, Scheifele M, Bui N, Patt M, et al. Assessment of perfusion deficit with early phases of [(18)F]PI-2620 tau-PET versus [(18)F]flutemetamol-amyloid-PET recordings. Eur J Nucl Med Mol Imaging. 2023;50:1384–94.
pubmed: 36572740
doi: 10.1007/s00259-022-06087-y
Lyoo CH, Ikawa M, Liow JS, Zoghbi SS, Morse CL, Pike VW, et al. Cerebellum can serve as a pseudo-reference region in alzheimer disease to detect neuroinflammation measured with PET radioligand binding to translocator protein. J Nucl Med. 2015;56:701–6.
pubmed: 25766898
doi: 10.2967/jnumed.114.146027
Cho SH, Choe YS, Park S, Kim YJ, Kim HJ, Jang H, et al. Appropriate reference region selection of (18)F-florbetaben and (18)F-flutemetamol beta-amyloid PET expressed in Centiloid. Sci Rep. 2020;10:14950.
pubmed: 32917930
pmcid: 7486392
doi: 10.1038/s41598-020-70978-z
Fan L, Li H, Zhuo J, Zhang Y, Wang J, Chen L, et al. The human brainnetome atlas: a new brain atlas based on connectional architecture. Cereb Cortex. 2016;26:3508–26.
pubmed: 27230218
pmcid: 4961028
doi: 10.1093/cercor/bhw157
Kolabas ZI, Kuemmerle LB, Perneczky R, Förstera B, Büttner M, Caliskan OS, et al. Multi-omics and 3D-imaging reveal bone heterogeneity and unique calvaria cells in neuroinflammation. Cell. 2023. In press.
Katzdobler S, Nitschmann A, Barthel H, Bischof G, Beyer L, Marek K, et al. Additive value of [(18)F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome. Eur J Nucl Med Mol Imaging. 2023;50:423–34.
pubmed: 36102964
doi: 10.1007/s00259-022-05964-w
Owen DR, Gunn RN, Rabiner EA, Bennacef I, Fujita M, Kreisl WC, et al. Mixed-affinity binding in humans with 18-kDa translocator protein ligands. J Nucl Med. 2011;52:24–32.
pubmed: 21149489
doi: 10.2967/jnumed.110.079459
Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012;32:1–5.
pubmed: 22008728
doi: 10.1038/jcbfm.2011.147
Kleinberger G, Yamanishi Y, Suarez-Calvet M, Czirr E, Lohmann E, Cuyvers E, et al. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci Transl Med. 2014;6:243ra86.
pubmed: 24990881
doi: 10.1126/scitranslmed.3009093
Suarez-Calvet M, Morenas-Rodriguez E, Kleinberger G, Schlepckow K, Araque Caballero MA, Franzmeier N, et al. Early increase of CSF sTREM2 in Alzheimer’s disease is associated with tau related-neurodegeneration but not with amyloid-beta pathology. Mol Neurodegener. 2019;14:1.
pubmed: 30630532
pmcid: 6327425
doi: 10.1186/s13024-018-0301-5
Morenas-Rodriguez E, Li Y, Nuscher B, Franzmeier N, Xiong C, Suarez-Calvet M, et al. Soluble TREM2 in CSF and its association with other biomarkers and cognition in autosomal-dominant Alzheimer’s disease: a longitudinal observational study. Lancet Neurol. 2022;21:329–41.
pubmed: 35305339
pmcid: 8926925
doi: 10.1016/S1474-4422(22)00027-8
Golbe LI, Ohman-Strickland PA. A clinical rating scale for progressive supranuclear palsy. Brain. 2007;130:1552–65.
pubmed: 17405767
doi: 10.1093/brain/awm032
Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, et al. Movement disorder society-sponsored revision of the unified parkinson’s disease rating scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008;23:2129–70.
pubmed: 19025984
doi: 10.1002/mds.22340
Sheikh J, Yesavage JA. Geriatric depression scale (GDS): recent evidence and development of a shorter version. Clin Gerontol. 1986;5:165–73.
doi: 10.1300/J018v05n01_09
Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005;53:695–9.
pubmed: 15817019
doi: 10.1111/j.1532-5415.2005.53221.x
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.
pubmed: 1202204
doi: 10.1016/0022-3956(75)90026-6
Bergeron D, Flynn K, Verret L, Poulin S, Bouchard RW, Bocti C, et al. Multicenter validation of an MMSE-MoCA conversion table. J Am Geriatr Soc. 2017;65:1067–72.
pubmed: 28205215
doi: 10.1111/jgs.14779
Vettermann FJ, Harris S, Schmitt J, Unterrainer M, Lindner S, Rauchmann BS, et al. Impact of TSPO Receptor Polymorphism on [(18)F]GE-180 Binding in Healthy Brain and Pseudo-Reference Regions of Neurooncological and Neurodegenerative Disorders. Life (Basel). 2021;11:484.
pubmed: 34073557
Metz CE. Basic principles of ROC analysis. Semin Nucl Med. 1978;8:283–98.
pubmed: 112681
doi: 10.1016/S0001-2998(78)80014-2
Vermont J, Bosson J-L, François P, Robert C, Rueff A, Demongeot J. Strategies for graphical threshold determination. Comput Methods Programs Biomed. 1991;35:141–50.
pubmed: 1914452
doi: 10.1016/0169-2607(91)90072-2
Brainnetome parcellation ( http://atlas.brainnetome.org/bnatlas.html ).
Vogel JW, Young AL, Oxtoby NP, Smith R, Ossenkoppele R, Strandberg OT, et al. Four distinct trajectories of tau deposition identified in Alzheimer’s disease. Nat Med. 2021;27:871–81.
pubmed: 33927414
pmcid: 8686688
doi: 10.1038/s41591-021-01309-6
Kreisl WC. Discerning the relationship between microglial activation and Alzheimer’s disease. Brain. 2017;140:1825–8.
pubmed: 29177498
doi: 10.1093/brain/awx151
Eckenweber F, Medina-Luque J, Blume T, Sacher C, Biechele G, Wind K, et al. Longitudinal TSPO expression in tau transgenic P301S mice predicts increased tau accumulation and deteriorated spatial learning. J Neuroinflammation. 2020;17:208.
pubmed: 32660586
pmcid: 7358201
doi: 10.1186/s12974-020-01883-5
Zou J, Tao S, Johnson A, Tomljanovic Z, Polly K, Klein J, et al. Microglial activation, but not tau pathology, is independently associated with amyloid positivity and memory impairment. Neurobiol Aging. 2020;85:11–21.
pubmed: 31698286
doi: 10.1016/j.neurobiolaging.2019.09.019
Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med. 2015;3:136.
pubmed: 26207229
pmcid: 4486922
Bamberger ME, Harris ME, McDonald DR, Husemann J, Landreth GE. A cell surface receptor complex for fibrillar beta-amyloid mediates microglial activation. J Neurosci. 2003;23:2665–74.
pubmed: 12684452
pmcid: 6742111
doi: 10.1523/JNEUROSCI.23-07-02665.2003
Blume T, Focke C, Peters F, Deussing M, Albert NL, Lindner S, et al. Microglial response to increasing amyloid load saturates with aging: a longitudinal dual tracer in vivo muPET-study. J Neuroinflammation. 2018;15:307.
pubmed: 30400912
pmcid: 6220478
doi: 10.1186/s12974-018-1347-6
Franzmeier N, Brendel M, Beyer L, Slemann L, Kovacs GG, Arzberger T, et al. Tau deposition patterns are associated with functional connectivity in primary tauopathies. Nat Commun. 2022;13:1362.
pubmed: 35292638
pmcid: 8924216
doi: 10.1038/s41467-022-28896-3
Ismail R, Parbo P, Madsen LS, Hansen AK, Hansen KV, Schaldemose JL, et al. The relationships between neuroinflammation, beta-amyloid and tau deposition in Alzheimer’s disease: a longitudinal PET study. J Neuroinflammation. 2020;17:151.
pubmed: 32375809
pmcid: 7203856
doi: 10.1186/s12974-020-01820-6
Toppala S, Ekblad LL, Tuisku J, Helin S, Johansson JJ, Laine H, et al. Association of early beta-amyloid accumulation and neuroinflammation measured with [(11)C]PBR28 in elderly individuals without dementia. Neurology. 2021;96:e1608–e19.
pubmed: 33514647
pmcid: 8032368
doi: 10.1212/WNL.0000000000011612
Beyer L, Meyer-Wilmes J, Schonecker S, Schnabel J, Brendel E, Prix C, et al. Clinical routine FDG-PET imaging of suspected progressive supranuclear palsy and corticobasal degeneration: a gatekeeper for subsequent Tau-PET imaging? Front Neurol. 2018;9:483.
pubmed: 29973914
pmcid: 6019471
doi: 10.3389/fneur.2018.00483
Ising C, Venegas C, Zhang S, Scheiblich H, Schmidt SV, Vieira-Saecker A, et al. NLRP3 inflammasome activation drives tau pathology. Nature. 2019;575:669–73.
pubmed: 31748742
pmcid: 7324015
doi: 10.1038/s41586-019-1769-z
Ewers M, Franzmeier N, Suárez-Calvet M, Morenas-Rodriguez E, Caballero MAA, Kleinberger G, et al. Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer’s disease. Sci Transl Med. 2019;11:eaav6221.
pubmed: 31462511
pmcid: 7050285
doi: 10.1126/scitranslmed.aav6221
Lee SH, Meilandt WJ, Xie L, Gandham VD, Ngu H, Barck KH, et al. Trem2 restrains the enhancement of tau accumulation and neurodegeneration by β-amyloid pathology. Neuron. 2021;109:1283–301.e6.
pubmed: 33675684
doi: 10.1016/j.neuron.2021.02.010
Focke C, Blume T, Zott B, Shi Y, Deussing M, Peters F, et al. Early and longitudinal microglial activation but not amyloid accumulation predicts cognitive outcome in PS2APP mice. J Nucl Med. 2019;60:548–54.
pubmed: 30262517
doi: 10.2967/jnumed.118.217703
Blume T, Deussing M, Biechele G, Peters F, Zott B, Schmidt C, et al. Chronic PPARgamma stimulation shifts amyloidosis to higher fibrillarity but improves cognition. Front Aging Neurosci. 2022;14:854031.
pubmed: 35431893
pmcid: 9007038
doi: 10.3389/fnagi.2022.854031
Malpetti M, Kievit RA, Passamonti L, Jones PS, Tsvetanov KA, Rittman T, et al. Microglial activation and tau burden predict cognitive decline in Alzheimer’s disease. Brain. 2020;143:1588–602.
pubmed: 32380523
pmcid: 7241955
doi: 10.1093/brain/awaa088
Kroth H, Oden F, Molette J, Schieferstein H, Capotosti F, Mueller A, et al. Discovery and preclinical characterization of [(18)F]PI-2620, a next-generation tau PET tracer for the assessment of tau pathology in Alzheimer’s disease and other tauopathies. Eur J Nucl Med Mol Imaging. 2019;46:2178–89.
pubmed: 31264169
pmcid: 6667408
doi: 10.1007/s00259-019-04397-2
Mueller A, Bullich S, Barret O, Madonia J, Berndt M, Papin C, et al. Tau PET imaging with (18)F-PI-2620 in patients with Alzheimer disease and healthy controls: a first-in-humans study. J Nucl Med. 2020;61:911–9.
pubmed: 31712323
pmcid: 7262222
doi: 10.2967/jnumed.119.236224
Willroider M, Roeber S, Horn AKE, Arzberger T, Scheifele M, Respondek G, et al. Superiority of formalin-fixed paraffin-embedded brain tissue for in vitro assessment of progressive supranuclear palsy tau pathology with [(18) F]PI-2620. Front Neurol. 2021;12:684523.
pubmed: 34276540
pmcid: 8282895
doi: 10.3389/fneur.2021.684523
Kunze G, Kumpfel R, Rullmann M, Barthel H, Brendel M, Patt M, et al. Molecular simulations reveal distinct energetic and kinetic binding properties of [(18)F]PI-2620 on Tau filaments from 3R/4R and 4R Tauopathies. ACS Chem Neurosci. 2022;13:2222–34.
pubmed: 35762647
doi: 10.1021/acschemneuro.2c00291
Malarte ML, Gillberg PG, Kumar A, Bogdanovic N, Lemoine L, Nordberg A. Discriminative binding of tau PET tracers PI2620, MK6240 and RO948 in Alzheimer’s disease, corticobasal degeneration and progressive supranuclear palsy brains. Mol Psychiatry. 2023;28:1272–83.
pubmed: 36447011
doi: 10.1038/s41380-022-01875-2
Snellman A, Rokka J, Lopez-Picon FR, Eskola O, Wilson I, Farrar G, et al. Pharmacokinetics of [(1)(8)F]flutemetamol in wild-type rodents and its binding to beta amyloid deposits in a mouse model of Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2012;39:1784–95.
pubmed: 22801729
doi: 10.1007/s00259-012-2178-9
Zanotti-Fregonara P, Pascual B, Rostomily RC, Rizzo G, Veronese M, Masdeu JC, et al. Anatomy of (18)F-GE180, a failed radioligand for the TSPO protein. Eur J Nucl Med Mol Imaging. 2020;47:2233–6.
pubmed: 32088848
doi: 10.1007/s00259-020-04732-y
van Assema DM, Lubberink M, Bauer M, van der Flier WM, Schuit RC, Windhorst AD, et al. Blood-brain barrier P-glycoprotein function in Alzheimer’s disease. Brain. 2012;135:181–9.
pubmed: 22120145
doi: 10.1093/brain/awr298
de Vries HE, Kuiper J, de Boer AG, Van Berkel TJ, Breimer DD. The blood-brain barrier in neuroinflammatory diseases. Pharmacol Rev. 1997;49:143–55.
pubmed: 9228664