Abstract
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.
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This post is Copyright: Johannes Levin,
Simone Baiardi,
Corinne Quadalti,
Marcello Rossi,
Angela Mammana,
Jonathan Vöglein,
Alexander Bernhardt,
Richard J. Perrin,
Mathias Jucker,
Oliver Preische,
Anna Hofmann,
Günter U. Höglinger,
Nigel J. Cairns,
Erin E. Franklin,
Patricio Chrem,
Carlos Cruchaga,
Sarah B. Berman,
Jasmeer P. Chhatwal,
Alisha Daniels,
Gregory S. Day,
Natalie S. Ryan,
Alison M. Goate,
Brian A. Gordon,
Edward D. Huey,
Laura Ibanez,
Celeste M. Karch,
Jae‐Hong Lee,
Jorge Llibre‐Guerra,
Francisco Lopera,
Colin L. Masters,
John C. Morris,
James M. Noble,
Alan E. Renton,
Jee Hoon Roh,
Matthew P. Frosch,
C. Dirk Keene,
Catriona McLean,
Raquel Sanchez‐Valle,
Peter R. Schofield,
Charlene Supnet‐Bell,
Chengjie Xiong,
Armin Giese,
Oskar Hansson,
Randall J. Bateman,
Eric McDade,
Dominantly Inherited Alzheimer Network,
Piero Parchi | April 26, 2024