SV2A PET shows hippocampal synaptic loss in cognitively unimpaired APOE ε4/ε4 homozygotes.
Alzheimer's disease
[11C]UCB‐J
amyloid beta
apolipoprotein E
biomarker
cognition
hippocampus
positron emission tomography
preclinical
synaptic density
synaptic vesicle 2A
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
revised:
15
09
2024
received:
08
03
2024
accepted:
21
09
2024
medline:
30
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
aheadofprint
Résumé
We investigated hippocampal synaptic density using synaptic vesicle 2A positron emission tomography (PET), and its association with amyloid beta (Aβ) and cognitive performance in healthy apolipoprotein E (APOE) ε4 carriers. Synaptic density was assessed in 46 individuals (APOE ε4/ε4 n = 14; APOE ε3/ε4 n = 16; APOE ε3/ε3 n = 16) with [ Hippocampal synaptic density was different among the APOE groups (P Hippocampal synaptic loss emerges early in the AD continuum and is measurable in vivo in cognitively unimpaired high-risk individuals. Synaptic density was studied in vivo in healthy older adults using [
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Finnish Governmental Research Funding (VTR)
Organisme : Research Council of Finland
ID : 341059
Organisme : Emil Aaltonen Foundation
Organisme : Paulo Foundation
Organisme : Orion Research Foundation
Organisme : Sigrid Juselius Foundation
Informations de copyright
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
Masliah E, Mallory M, Alford M, et al. Altered expression of synaptic proteins occurs early during progression of Alzheimer's disease. Neurology. 2001;56(1):127‐129.
Scheff SW, Price DA, Schmitt FA, Mufson EJ. Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment. Neurobiol Aging. 2006;27(10):1372‐1384. doi:10.1016/j.neurobiolaging.2005.09.012
Scheff SW, Ansari MA, Mufson EJ. Oxidative stress and hippocampal synaptic protein levels in elderly cognitively intact individuals with Alzheimer's disease pathology. Neurobiol Aging. 2016;42:1‐12. doi:10.1016/j.neurobiolaging.2016.02.030
Terry RD, Masliah E, Salmon DP, et al. Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol. 1991;30(4):572‐580. doi:10.1002/ana.410300410
Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261(5123):921‐923.
Love S, Siew LK, Dawbarn D, Wilcock GK, Ben‐Shlomo Y, SJ Allen. Premorbid effects of APOE on synaptic proteins in human temporal neocortex. Neurobiol Aging. 2006;27(6):797‐803. doi:10.1016/j.neurobiolaging.2005.04.008
Butt OH, Long JM, Henson RL, et al. Cognitively normal APOE ε4 carriers have specific elevation of CSF SNAP‐25. Neurobiol Aging. 2021;102:64‐72. doi:10.1016/j.neurobiolaging.2021.02.008
Dumanis SB, Tesoriero JA, Babus LW, et al. ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo. J Neurosci. 2009;29(48):15317‐15322. doi:10.1523/JNEUROSCI.4026‐09.2009
Blennow K. A review of fluid biomarkers for Alzheimer's disease: moving from CSF to blood. Neurol Ther. 2017;6(Suppl 1):15‐24. doi:10.1007/s40120‐017‐0073‐9
Finnema SJ, Nabulsi NB, Eid T, et al. Imaging synaptic density in the living human brain. Sci Transl Med. 2016;8(348):348ra96. doi:10.1126/scitranslmed.aaf6667
Finnema SJ, Nabulsi NB, Mercier J, et al. Kinetic evaluation and test‐retest reproducibility of [11C]UCB‐J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. J Cereb Blood Flow Metab. 2018;38(11):2041‐2052. doi:10.1177/0271678X17724947
Bajjalieh SM, Frantz GD, Weimann JM, McConnell SK, Scheller RH. Differential expression of synaptic vesicle protein 2 (SV2) isoforms. J Neurosci. 1994;14(9):5223‐5235.
Varnäs K, Stepanov V, Halldin C. Autoradiographic mapping of synaptic vesicle glycoprotein 2A in non‐human primate and human brain. Synapse. 2020;74(10):e22157. doi:10.1002/syn.22157
Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp. 2011;70(11):960‐969. doi:10.1097/NEN.0b013e318232a379
Mecca AP, O'Dell RS, Sharp ES, et al. Synaptic density and cognitive performance in Alzheimer's disease: a PET imaging study with [11 C]UCB‐J. Alzheimers Dement. 2022;18(12):2527‐2536. doi:10.1002/alz.12582
Chen MK, Mecca AP, Naganawa M, et al. Assessing synaptic density in Alzheimer disease with synaptic vesicle glycoprotein 2A positron emission tomographic imaging. JAMA Neurol. 2018;75(10):1215‐1224. doi:10.1001/jamaneurol.2018.1836
Mecca AP, Chen MK, O'Dell RS, et al. In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET. Alzheimers Dementia. 2020;16(7):974‐982. doi:10.1002/alz.12097
Vanhaute H, Ceccarini J, Michiels L, et al. In vivo synaptic density loss is related to tau deposition in amnestic mild cognitive impairment. Neurology. 2020;95(5):e545‐e553. doi:10.1212/WNL.0000000000009818
Bastin C, Bahri MA, Meyer F, et al. In vivo imaging of synaptic loss in Alzheimer's disease with [18F]UCB‐H positron emission tomography. Eur J Nucl Med Mol Imaging. 2020;47(2):390‐402. doi:10.1007/s00259‐019‐04461‐x
O'Dell RS, Mecca AP, Chen MK, et al. Association of Aβ deposition and regional synaptic density in early Alzheimer's disease: a PET imaging study with [11C]UCB‐J. Alzheimers Res Ther. 2021;13(1):1758‐9193. doi:10.1186/s13195‐020‐00742‐y
Snellman A, Ekblad LL, Koivumäki M, et al. ASIC‐E4: interplay of beta‐amyloid, synaptic density and neuroinflammation in cognitively normal volunteers with three levels of genetic risk for late‐onset Alzheimer's disease—study protocol and baseline characteristics. Front Neurol. 2022;13:826423. doi:10.3389/fneur.2022.826423
Krzyczmonik A, Wahlroos S, Helin S, Kirjavainen A, Solin O. P‐141 ‐ Long term experience in [11C]UCB‐J production in Turku PET Centre. Nuclear Medicine and Biology;. 2022;108‐109:S126‐S127.
Nabulsi NB, Mercier J, Holden D, et al. Synthesis and preclinical evaluation of [11C]UCB‐J as a PET tracer for imaging the synaptic vesicle glycoprotein 2A in the brain. J Nucl Med. 2016;57(5):777‐784. doi:10.2967/jnumed.115.168179
Nabulsi N, Hannestad J, Holden D, et al. [11C]UCB‐J: a novel PET tracer for imaging the synaptic vesicle glycoprotein 2A (SV2A). 2014;55(Suppl 1):355.
Onega M, Chong H, Roble A, et al. Highly improved and GMP compliant synthesis of [11C]UCB‐J: in situ generation of boronic acid precursor. Eur J Nucl Med Mol Imaging. 2017:S528.
Sureau FC, Reader AJ, Comtat C, et al. Impact of image‐space resolution modeling for studies with the high‐resolution research tomograph. J Nucl Med. 2008;49(6):1000‐1008. doi:10.2967/jnumed.107.045351
Comtat C, Sureau FC, Sibomana M, Hong IK, Sjoholm N, Trebossen R. Image based resolution modeling for the HRRT OSEM reconstructions software. IEEE Nuclear Science Symposium Conference Record. 2008:4120‐4123. doi:10.1109/NSSMIC.2008.4774188
Snellman A, Ekblad L, Tuisku J, et al. APOE ε4 gene dose effect on imaging and blood biomarkers of neuroinflammation and beta‐amyloid in cognitively unimpaired elderly. Alzheimers Res Ther. 2023;15(1):71. doi:10.1186/s13195‐023‐01209‐6
Karjalainen T, Tuisku J, Santavirta S, et al. Magia: robust automated image processing and kinetic modeling toolbox for PET neuroinformatics. Front Neuroinform. 2020;14:3. doi:10.3389/fninf.2020.00003
Naganawa M, Gallezot JD, Finnema SJ, et al. Simplified quantification of [11C]UCB‐J PET evaluated in a large human cohort. J Nucl Med. 2021;62(3):418‐421. doi:10.2967/jnumed.120.243949
Koole M, van Aalst J, Devrome M, et al. Quantifying SV2A density and drug occupancy in the human brain using [11C]UCB‐J PET imaging and subcortical white matter as reference tissue. Eur J Nucl Med Mol Imaging. 2019;46(2):396‐406. doi:10.1007/s00259‐018‐4119‐8
Rossano S, Toyonaga T, Finnema SJ, et al. Assessment of a white matter reference region for [11C]UCB‐J PET quantification. J Cereb Blood Flow Metab. 2020;40(9):1890‐1901. doi:10.1177/0271678X19879230
Randolph C, Tierney MC, Mohr E, Chase TN. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998;20(3):310‐319. doi:10.1076/jcen.20.3.310.823
Chandler MJ, Lacritz LH, Hynan LS, et al. A total score for the CERAD neuropsychological battery. Neurology. 2005;65(1):102‐106. doi:10.1212/01.wnl.0000167607.63000.38
Langbaum JB, Ellison NN, Caputo A, et al. The Alzheimer's Prevention Initiative Composite Cognitive Test: a practical measure for tracking cognitive decline in preclinical Alzheimer's disease. Alzheimers Res Ther. 2020;12(1):66. doi:10.1186/s13195‐020‐00633‐2
Gómez‐Isla T, Price JL, McKeel DW, Morris JC, Growdon JH, Hyman BT. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J Neurosci. 1996;16(14):4491‐4500. doi:10.1523/JNEUROSCI.16‐14‐04491.1996
Varrone A, Sjöholm N, Eriksson L, Gulyás B, Halldin C, Farde L. Advancement in PET quantification using 3D‐OP‐OSEM point spread function reconstruction with the HRRT. Eur J Nucl Med Mol Imaging. 2009;36(10):1639‐1650. doi:10.1007/s00259‐009‐1156‐3
Tannenberg RK, Scott HL, Tannenberg AE, Dodd PR. Selective loss of synaptic proteins in Alzheimer's disease: evidence for an increased severity with APOE varepsilon4. Neurochem Int. 2006;49(7):631‐639. doi:10.1016/j.neuint.2006.05.004
Wang S, Zhang J, Pan T. APOE ε4 is associated with higher levels of CSF SNAP‐25 in prodromal Alzheimer's disease. Neurosci Lett. 2018;685:109‐113. doi:10.1016/j.neulet.2018.08.029
Sun X, Dong C, Levin B, et al. APOE ε4 carriers may undergo synaptic damage conferring risk of Alzheimer's disease. Alzheimers Dement. 2016;12(11):1159‐1166. doi:10.1016/j.jalz.2016.05.003
Robinson JL, Molina‐Porcel L, Corrada MM, et al. Perforant path synaptic loss correlates with cognitive impairment and Alzheimer's disease in the oldest‐old. Brain. 2014;137(Pt 9):2578‐2587. doi:10.1093/brain/awu190
DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol. 1990;27(5):457‐464. doi:10.1002/ana.410270502
Mendoza‐Torreblanca JG, Vanoye‐Carlo A, Phillips‐Farfan BV, Carmona‐Aparicio L, Gomez‐Lira G. Synaptic vesicle protein 2A: basic facts and role in synaptic function. Eur J Neurosci. 2013;38(11):3529‐3539. doi:10.1111/ejn.12360
Kumar A, Scarpa M, Nordberg A. Tracing synaptic loss in Alzheimer's brain with SV2A PET‐tracer UCB‐J. Alzheimers Dement. 2024;20(4):2589‐2605. doi:10.1002/alz.13720
Coomans EM, Schoonhoven DN, Tuncel H, et al. In vivo tau pathology is associated with synaptic loss and altered synaptic function. Alzheimers Res Ther. 2021;13(1):35. doi:10.1186/s13195‐021‐00772‐0