Journal Article

DZNE-2024-00783

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 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.

Levin, J. (First author)DZNE* ; Baiardi, S. ; Quadalti, C. ; Rossi, M. ; Mammana, A. ; Vöglein, J.DZNE* ; Bernhardt, A.DZNE* ; Perrin, R. J. ; Jucker, M.DZNE* ; Preische, O.DZNE* ; Hofmann, A.DZNE* ; Höglinger, G. U.DZNE* ; Cairns, N. J. ; Franklin, E. E. ; Chrem, P. ; Cruchaga, C. ; Berman, S. B. ; Chhatwal, J. P. ; Daniels, A. ; Day, G. S. ; Ryan, N. S. ; Goate, A. M. ; Gordon, B. A. ; Huey, E. D. ; Ibanez, L. ; Karch, C. M. ; Lee, J.-H. ; Llibre-Guerra, J. ; Lopera, F. ; Masters, C. L. ; Morris, J. C. ; Noble, J. M. ; Renton, A. E. ; Roh, J. H. ; Frosch, M. P. ; Keene, C. D. ; McLean, C. ; Sanchez-Valle, R. ; Schofield, P. R. ; Supnet-Bell, C. ; Xiong, C. ; Giese, A. ; Hansson, O. ; Bateman, R. J. ; McDade, E. ; Network, D. I. A. (Collaboration Author) ; Parchi, P.

2024
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.13818

Abstract: 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.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.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.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.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.

Keyword(s): Alzheimer Disease: diagnosis (MeSH) ; Humans (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: cerebrospinal fluid (MeSH) ; alpha-Synuclein: cerebrospinal fluid (MeSH) ; alpha-Synuclein: genetics (MeSH) ; Female (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Lewy Bodies: pathology (MeSH) ; Aged (MeSH) ; Mutation (MeSH) ; Brain: pathology (MeSH) ; Amyloid beta-Peptides: cerebrospinal fluid (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Disease Progression (MeSH) ; alpha‐synuclein seed amplification assay ; Dominantly Inherited Alzheimer Network ; Lewy body pathology ; alpha‐synuclein seed amplification assay ; real‐time quaking‐induced conversion ; alpha-Synuclein ; Amyloid beta-Peptides ; real‐time quaking‐induced conversion

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Contributing Institute(s):

1. Clinical Research (Munich) (Clinical Research (Munich))
2. Cell Biology of Neurological Diseases (AG Jucker)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Experiment(s):

1. Longitudinal Study on Dominantly Inherited Alzheimer's Disease

Appears in the scientific report 2024

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Database coverage:
; ; ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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