Contribution of alpha-synuclein pathology to cerebral glucose metabolism in patients with amnestic MCI.
Alzheimer's disease
Lewy body disease
PET
biomarker
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:
23 Aug 2024
23 Aug 2024
Historique:
revised:
21
06
2024
received:
03
05
2024
accepted:
02
07
2024
medline:
23
8
2024
pubmed:
23
8
2024
entrez:
23
8
2024
Statut:
aheadofprint
Résumé
The in vivo detection of mixed Alzheimer's disease (AD) and α-synuclein (αSyn) pathology is important for clinical management and prognostic stratification. We investigated the contribution of αSyn pathology, detected by cerebrospinal fluid (CSF) seed amplification assay (αSyn SAA), on [18F]-fluorodeoxyglucose positron emission tomography (FDG PET) pattern in subjects with amnestic mild cognitive impairment (aMCI). We included 562 aMCI participants and 204 cognitively normal controls (CN) with available αSyn SAA and cerebral metabolic rate for glucose utilization (rCMRgl) data. 24% of aMCI cases were positive (+) for CSF αSyn SAA. Compared to CN, both αSyn+ and negative (-) aMCI participants showed reductions in rCMRgl within AD typical regions. αSyn+ aMCI had lower rCMRgl within AD and dementia with Lewy bodies (DLB) typical regions compared to αSyn- aMCI, even after stratification according to the CSF AT(N) system. αSyn pathology contributes to a distinct FDG PET pattern in aMCI. αSyn pathology can be detected in vivo by CSF αSyn SAA. We investigated the FDG PET pattern in aMCI patients with CSF αSyn SAA positivity. αSyn+ aMCI showed a marked brain hypometabolism in AD and DLB typical regions.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : U01 AG024904
Pays : United States
Organisme : Medical Faculty of Martin-Luther-University of Halle-Wittenberg
ID : CS22/06
Organisme : German Federal Ministry of Education and Research
ID : FTLDc 01GI1007A
Informations de copyright
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
Albert MS, DeKosky ST, Dickson D, 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. 2011;7:270‐279. doi:10.1016/j.jalz.2011.03.008
Roberts R, Knopman DS. Classification and epidemiology of MCI. Clin Geriatr Med. 2013;29:753‐772. doi:10.1016/j.cger.2013.07.003
Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA. The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol. 2009;66:200‐208. doi:10.1002/ana.21706
Dugger BN, Davis K, Malek‐Ahmadi M, et al. Neuropathological comparisons of amnestic and nonamnestic mild cognitive impairment. BMC Neurol. 2015;15:146. doi:10.1186/s12883‐015‐0403‐4
McKeith IG, Ferman TJ, Thomas AJ, et al. Research criteria for the diagnosis of prodromal dementia with Lewy bodies. Neurology. 2020;94:743‐755. doi:10.1212/WNL.0000000000009323
Donaghy PC, Carrarini C, Ferreira D, et al. Research diagnostic criteria for mild cognitive impairment with Lewy bodies: a systematic review and meta‐analysis. Alzheimers Dement. 2023;19:3186‐3202. doi:10.1002/alz.13105
Kapasi A, DeCarli C, Schneider JA. Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathol. 2017;134:171‐186. doi:10.1007/s00401‐017‐1717‐7
Irwin DJ, Grossman M, Weintraub D, et al. Neuropathological and genetic correlates of survival and dementia onset in synucleinopathies: a retrospective analysis. Lancet Neurol. 2017;16:55‐65. doi:10.1016/S1474‐4422(16)30291‐5
Rabinovici GD, Carrillo MC, Forman M, et al. Multiple comorbid neuropathologies in the setting of Alzheimer's disease neuropathology and implications for drug development. Alzheimers Dement. 2017;3:83‐91. doi:10.1016/j.trci.2016.09.002
DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer's disease. Mol Neurodegener. 2019;14:32. doi:10.1186/s13024‐019‐0333‐5
Ferman TJ, Aoki N, Boeve BF, et al. Subtypes of dementia with Lewy bodies are associated with α‐synuclein and tau distribution. Neurology. 2020;95:e155‐e165. doi:10.1212/WNL.0000000000009763
Spina S, La Joie R, Petersen C, et al. Comorbid neuropathological diagnoses in early versus late‐onset Alzheimer's disease. Brain. 2021;144:2186‐2198. doi:10.1093/brain/awab099
Weisman D, Cho M, Taylor C, Adame A, Thal LJ, Hansen LA. In dementia with Lewy bodies, Braak stage determines phenotype, not Lewy body distribution. Neurology. 2007;69:356‐359. doi:10.1212/01.wnl.0000266626.64913.0f
Sim J, Li H, Hameed S, Ting SKS. Clinical manifestations of early‐onset dementia with Lewy bodies compared with late‐onset dementia with Lewy bodies and early‐onset Alzheimer disease. JAMA Neurol. 2022;79:702‐709. doi:10.1001/jamaneurol.2022.1133
van de Beek M, Ooms FAH, Ebenau JL, et al. Association of the ATN research framework with clinical profile, cognitive decline, and mortality in patients with dementia with Lewy bodies. Neurology. 2022;98:e1262‐e1272. doi:10.1212/WNL.0000000000200048
Quadalti C, Palmqvist S, Hall S, et al. Clinical effects of Lewy body pathology in cognitively impaired individuals. Nat Med. 2023;29:1964‐1970. doi:10.1038/s41591‐023‐02449‐7
Jack CR, Bennett DA, Blennow K, et al. NIA‐AA Research Framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14:535‐562. doi:10.1016/j.jalz.2018.02.018
Barba L, Abu‐Rumeileh S, Halbgebauer S, et al. CSF synaptic biomarkers in AT(N)‐based subgroups of Lewy body disease. Neurology. 2023;101:e50‐e62. doi:10.1212/WNL.0000000000207371
Arbizu J, Festari C, Altomare D, et al. Clinical utility of FDG‐PET for the clinical diagnosis in MCI. Eur J Nucl Med Mol Imaging. 2018;45:1497‐1508. doi:10.1007/s00259‐018‐4039‐7
Rossi M, Baiardi S, Teunissen CE, et al. Diagnostic value of the CSF α‐Synuclein real‐time quaking‐induced conversion assay at the prodromal MCI stage of dementia with Lewy bodies. Neurology. 2021;97:e930‐e940. doi:10.1212/WNL.0000000000012438
Pilotto A, Bongianni M, Tirloni C, Galli A, Padovani A, Zanusso G. CSF alpha‐synuclein aggregates by seed amplification and clinical presentation of AD. Alzheimers Dement. 2023;19:3754‐3759. doi:10.1002/alz.13109
Bellomo G, Toja A, Paolini Paoletti F, et al. Investigating alpha‐synuclein co‐pathology in Alzheimer's disease by means of cerebrospinal fluid alpha‐synuclein seed amplification assay. Alzheimers Dement. 2024;20(4):2444‐2452. doi:10.1002/alz.13658
ADNI Alzheimer's disease neuroimaging initiative ‐ homepage. ADNI. Accessed May 2, 2024. https://adni.loni.usc.edu
Amprion diagnostics ‐ homepage. Amprion diagnostics. Accessed May 2, 2024.https://ampriondx.com/Last
Arnold MR, Coughlin DG, Brumbach BH, et al. α‐Synuclein seed amplification in CSF and brain from patients with different brain distributions of pathological α‐Synuclein in the context of co‐pathology and non‐LBD diagnoses. Ann Neurol. 2022;92:650‐662. doi:10.1002/ana.26453
Landau SM, Lee J, Murphy A, et al. Individuals with Alzheimer's disease and low tau burden: characteristics and implications. Alzheimers Demen. 2024;20:2113‐2127. doi:10.1002/alz.13609
Shaw LM, Vanderstichele H, Knapik‐Czajka M, et al. Cerebrospinal fluid biomarker signature in Alzheimer's Disease Neuroimaging Initiative subjects. Ann Neurol. 2009;65:403‐413. doi:10.1002/ana.21610
SPM (Statistical parametric mapping). Wellcome Centre for Human Neuroimaging, UCL, London. Accessed May 2, 2024. https://www.fil.ion.ucl.ac.uk/spm‐statistical‐parametric‐mapping/
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;12:189‐198. doi:10.1016/0022‐3956(75)90026‐6
Skinner J, Carvalho JO, Potter GG, et al. The Alzheimer's Disease Assessment Scale‐Cognitive‐Plus (ADAS‐Cog‐Plus): an expansion of the ADAS‐Cog to improve responsiveness in MCI. Brain Imaging Behav. 2012;6:489‐501. doi:10.1007/s11682‐012‐9166‐3
Kaufer DI, Cummings JL, Ketchel P, et al. Validation of the NPI‐Q, a brief clinical form of the neuropsychiatric inventory. J Neuropsychiatry Clin Neurosci. 2000;12:233‐239. doi:10.1176/jnp.12.2.233
Threshold Free Cluster Enhancement (TFCE) toolbox index. University of Jena. Accessed May 2, 2024. https://www.neuro.uni‐jena.de/tfce/
MRIcron software Index. University of South Carolina. Accessed May 2, 2024. https://people.cas.sc.edu/rorden/mricron/index.HTML
Caminiti SP, Sala A, Iaccarino L, et al. Brain glucose metabolism in Lewy body dementia: implications for diagnostic criteria. Alzheimers Res Ther. 2019;11:20. doi:10.1186/s13195‐019‐0473‐4
Barba L, Abu‐Rumeileh S, Barthel H, et al. Clinical and diagnostic implications of Alzheimer's disease copathology in Lewy body disease. Brain. 2024 Jul 11:awae203. doi:10.1093/brain/awae203
Massa F, Chincarini A, Bauckneht M, et al. Added value of semiquantitative analysis of brain FDG‐PET for the differentiation between MCI‐Lewy bodies and MCI due to Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2022;49:1263‐1274. doi:10.1007/s00259‐021‐05568‐w
Mattioli P, Pardini M, Girtler N, et al. Cognitive and brain metabolism profiles of mild cognitive impairment in prodromal alpha‐synucleinopathy. J Alzheimers Dis. 2022;90:433‐444. doi:10.3233/JAD‐220653
Cotta Ramusino M, Massa F, Festari C, et al. Diagnostic performance of molecular imaging methods in predicting the progression from mild cognitive impairment to dementia: an updated systematic review. Eur J Nucl Med Mol Imaging. 2024;51:1876‐1890. doi:10.1007/s00259‐024‐06631‐y
Lashley T, Holton JL, Gray E, et al. Cortical α‐synuclein load is associated with amyloid‐β plaque burden in a subset of Parkinson's disease patients. Acta Neuropathol. 2008;115:417‐425. doi:10.1007/s00401‐007‐0336‐0
Compta Y, Parkkinen L, O'Sullivan SS, et al. Lewy‐ and Alzheimer‐type pathologies in Parkinson's disease dementia: which is more important? Brain. 2011;134:1493‐1505. doi:10.1093/brain/awr031
Shim KH, Kang MJ, Youn YC, An SSA, Kim S. Alpha‐synuclein: a pathological factor with Aβ and tau and biomarker in Alzheimer's disease. Alzheimers Res Ther. 2022;14:201. doi:10.1186/s13195‐022‐01150‐0
Ting SKS, Saffari SE, Hameed S, Chiew HJ, Ng KP, Ng AS. Clinical characteristics of pathological confirmed prodromal dementia with Lewy bodies. J Neurol Sci. 2023;453:120815. doi:10.1016/j.jns.2023.120815
Payne S, Shofer JB, Shutes‐David A, et al. Correlates of conversion from mild cognitive impairment to dementia with Lewy bodies: data from the National Alzheimer's Coordinating Center. J Alzheimers Dis. 2022;86:1643‐1654. doi:10.3233/JAD‐215428
Mintun MA, Lo AC, Duggan Evans C, et al. Donanemab in early Alzheimer's disease. N Engl J Med. 2021;384:1691‐1704. doi:10.1056/NEJMoa2100708
van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in early Alzheimer's disease. N Engl J Med. 2023;388:9‐21. doi:10.1056/NEJMoa2212948
Cummings J. Lessons learned from Alzheimer disease: clinical trials with negative outcomes. Clin Transl Sci. 2018;11:147‐152. doi:10.1111/cts.12491
Siderowf A, Aarsland D, Mollenhauer B, Goldman JG, Ravina B. Biomarkers for cognitive impairment in Lewy body disorders: status and relevance for clinical trials. Mov Disord. 2018;33:528‐536. doi:10.1002/mds.27355