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000279350 0247_ $$2doi$$a10.1002/alz.70342
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000279350 041__ $$aEnglish
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000279350 1001_ $$0P:(DE-2719)9002620$$aBernhardt, Alexander Maximilian$$b0$$eFirst author$$udzne
000279350 245__ $$aAlpha-synuclein co-pathology in Down syndrome-associated Alzheimer's disease.
000279350 260__ $$aHoboken, NJ$$bWiley$$c2025
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000279350 520__ $$aAlpha-synuclein (αSyn) seed amplification assay (SAA) enables in vivo study of αSyn but remains underexplored in Down syndrome-associated Alzheimer's disease (DSAD).We analyzed αSyn-SAA in cerebrospinal fluid (CSF) from 270 adults with Down syndrome, from the Down Alzheimer Barcelona Neuroimaging Initiative and from the AD21 cohort from the Department of Neurology at the University Hospital, Ludwig Maximilian University of Munich, Germany. Neuropathological examinations were conducted in 19 brain donors (five with ante mortem CSF). Participants were classified as asymptomatic or symptomatic (prodromal/dementia) Alzheimer's disease (AD). CSF Aβ1-42/1-40, CSF and plasma p-Tau181, and neurofilament light chain (NfL) levels were measured. Neuropathological evaluations assessed AD neuropathological changes and Lewy body pathology (LBP).ΑSyn-SAA was positive in 9.2% of cases, independent of age or cognitive status. Symptomatic αSyn-positive cases exhibited higher plasma NfL levels than αSyn-negative cases (31 vs 21 pg/mL, p = 0.027). LBP was observed in 47% of necropsies. The individual with severe neocortical LBP was αSyn-SAA-positive.These findings highlight LBP prevalence in DSAD but suggest current SAA may fail to detect limited αSyn deposition.αSyn-SAA positivity in DSAD is 9.2%, similar to ADAD but lower than sporadic AD. Misfolded αSyn was detectable from early ages in individuals with DS. Positivity rates did not vary with age or clinical status in DS. Plasma NfL levels are higher in symptomatic αSyn-SAA positive versus negative cases. CSF αSyn seeding activity was associated with high neocortical LBP at necropsy.
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000279350 650_7 $$2Other$$aAlzheimer's disease
000279350 650_7 $$2Other$$aDown syndrome
000279350 650_7 $$2Other$$aLewy body pathology
000279350 650_7 $$2Other$$abiomarker
000279350 650_7 $$2Other$$aneuropathology
000279350 650_7 $$2Other$$aseed amplification assay
000279350 650_7 $$2Other$$aα‐synuclein
000279350 650_7 $$2NLM Chemicals$$aalpha-Synuclein
000279350 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000279350 650_7 $$2NLM Chemicals$$aBiomarkers
000279350 650_7 $$2NLM Chemicals$$atau Proteins
000279350 650_7 $$2NLM Chemicals$$aNeurofilament Proteins
000279350 650_2 $$2MeSH$$aHumans
000279350 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000279350 650_2 $$2MeSH$$aAlzheimer Disease: cerebrospinal fluid
000279350 650_2 $$2MeSH$$aalpha-Synuclein: cerebrospinal fluid
000279350 650_2 $$2MeSH$$aDown Syndrome: pathology
000279350 650_2 $$2MeSH$$aDown Syndrome: complications
000279350 650_2 $$2MeSH$$aDown Syndrome: cerebrospinal fluid
000279350 650_2 $$2MeSH$$aFemale
000279350 650_2 $$2MeSH$$aMale
000279350 650_2 $$2MeSH$$aMiddle Aged
000279350 650_2 $$2MeSH$$aAged
000279350 650_2 $$2MeSH$$aAmyloid beta-Peptides: cerebrospinal fluid
000279350 650_2 $$2MeSH$$aBrain: pathology
000279350 650_2 $$2MeSH$$aBiomarkers: cerebrospinal fluid
000279350 650_2 $$2MeSH$$atau Proteins: cerebrospinal fluid
000279350 650_2 $$2MeSH$$atau Proteins: blood
000279350 650_2 $$2MeSH$$aAdult
000279350 650_2 $$2MeSH$$aNeurofilament Proteins: cerebrospinal fluid
000279350 650_2 $$2MeSH$$aNeurofilament Proteins: blood
000279350 7001_ $$00000-0003-3039-9115$$aRodríguez-Baz, Íñigo$$b1
000279350 7001_ $$aAldecoa, Iban$$b2
000279350 7001_ $$aArranz, Javier$$b3
000279350 7001_ $$aArriola-Infante, José Enrique$$b4
000279350 7001_ $$aMaure-Blesa, Lucia$$b5
000279350 7001_ $$aCarmona-Iragui, Maria$$b6
000279350 7001_ $$aLongen, Sebastian$$b7
000279350 7001_ $$aTrossbach, Svenja Verena$$b8
000279350 7001_ $$aGiese, Armin$$b9
000279350 7001_ $$aMatthias, Torsten$$b10
000279350 7001_ $$aBenejam, Bessy$$b11
000279350 7001_ $$aVidela, Laura$$b12
000279350 7001_ $$aDel Hoyo Soriano, Laura$$b13
000279350 7001_ $$aBarroeta, Isabel$$b14
000279350 7001_ $$aSanjuan, Aída$$b15
000279350 7001_ $$aFernández, Susana$$b16
000279350 7001_ $$aVaqué-Alcázar, Lídia$$b17
000279350 7001_ $$aRozalem Aranha, Mateus$$b18
000279350 7001_ $$aMorcillo-Nieto, Alejandra O$$b19
000279350 7001_ $$0P:(DE-2719)9001761$$aNübling, Georg$$b20$$udzne
000279350 7001_ $$0P:(DE-2719)9001249$$aWagemann, Olivia$$b21$$udzne
000279350 7001_ $$0P:(DE-2719)9002610$$aStockbauer, Anna$$b22$$udzne
000279350 7001_ $$aTondo, Mireia$$b23
000279350 7001_ $$aBejanin, Alexandre$$b24
000279350 7001_ $$aLleó, Alberto$$b25
000279350 7001_ $$aAlcolea, Daniel$$b26
000279350 7001_ $$aMolina-Porcel, Laura$$b27
000279350 7001_ $$aFortea, Juan$$b28
000279350 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b29$$eLast author$$udzne
000279350 773__ $$0PERI:(DE-600)2201940-6$$a10.1002/alz.70342$$gVol. 21, no. 6, p. e70342$$n6$$pe70342$$tAlzheimer's and dementia$$v21$$x1552-5260$$y2025
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