| Title: |
α-Synuclein seed amplification assay detects Lewy body co-pathology in autosomal dominant Alzheimer's disease late in the disease course and dependent on Lewy pathology burden |
| Authors: |
Levin, J; Baiardi, S; Quadalti, C; Rossi, M; Mammana, A; Vöglein, J; Bernhardt, A; Perrin, RJ; Jucker, M; Preische, O; Hofmann, A; Höglinger, GU; Cairns, NJ; Franklin, EE; Chrem, P; Cruchaga, C; Berman, SB; Chhatwal, JP; Daniels, A; Day, GS; Ryan, NS; Goate, AM; Gordon, BA; Huey, ED; Ibanez, L; Karch, CM; Lee, JH; Llibre-Guerra, J; Lopera, F; Masters, CL; Morris, JC; Noble, JM; Renton, AE; Roh, JH; Frosch, MP; Keene, CD; McLean, C; Sanchez-Valle, R; Schofield, PR; Supnet-Bell, C; Xiong, C; Giese, A; Hansson, O; Bateman, RJ; McDade, E; Parchi, P |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
INTRODUCTION: Amyloid beta and tau pathology are the hallmarks of sporadic Alzheimer's disease (AD) and autosomal dominant AD (ADAD). However, Lewy body pathology (LBP) is found in ≈ 50% of AD and ADAD brains. METHODS: Using an α-synuclein seed amplification assay (SAA) in cerebrospinal fluid (CSF) from asymptomatic (n = 26) and symptomatic (n = 27) ADAD mutation carriers, including 12 with known neuropathology, we investigated the timing of occurrence and prevalence of SAA positive reactivity in ADAD in vivo. RESULTS: No asymptomatic participant and only 11% (3/27) of the symptomatic patients tested SAA positive. Neuropathology revealed LBP in 10/12 cases, primarily affecting the amygdala or the olfactory areas. In the latter group, only the individual with diffuse LBP reaching the neocortex showed α-synuclein seeding activity in CSF in vivo. DISCUSSION: Results suggest that in ADAD LBP occurs later than AD pathology and often as amygdala- or olfactory-predominant LBP, for which CSF α-synuclein SAA has low sensitivity. HIGHLIGHTS: Cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC) detects misfolded α-synuclein in ≈ 10% of symptomatic autosomal dominant Alzheimer's disease (ADAD) patients. CSF RT-QuIC does not detect α-synuclein seeding activity in asymptomatic mutation carriers. Lewy body pathology (LBP) in ADAD mainly occurs as olfactory only or amygdala-predominant variants. LBP develops late in the disease course in ADAD. CSF α-synuclein RT-QuIC has low sensitivity for focal, low-burden LBP. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
1552-5260 |
| Relation: |
https://hdl.handle.net/11343/353820 |
| Availability: |
https://hdl.handle.net/11343/353820 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; CC BY |
| Accession Number: |
edsbas.434CC748 |
| Database: |
BASE |