Misfolded α-Synuclein in Autosomal Dominant Alzheimer’s Disease

Article type: Short Communication

Authors: Fort-Aznar, Laura^a | Molina-Porcel, Laura^{a; b} | Ramos-Campoy, Oscar^a | Esteller, Diana^a | Naranjo, Laura^c | Lladó, Albert^{a; d} | Balasa, Mircea^a | Ruiz-García, Raquel^c | Antonell, Anna^a | Sánchez-Valle, Raquel^{a; d; *}

Affiliations: [a] Alzheimer’s Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, FRCB-IDIBAPS, Barcelona, Spain | [b] Neurological Tissue Bank, Biobank-Hospital Clinic-FRCB-IDIBAPS, Barcelona, Spain | [c] Immunology Service, Biomedical Diagnostic Center, Hospital Clínic de Barcelona, Barcelona, Spain | [d] Facultat de Medicina i Ciències de la Salut, Institut de Neurociències, Universitat de Barcelona, Barcelona, Spain

Correspondence: [*] Correspondence to: Raquel S´nchez-Valle, MD, PhD, Alzheimer’s disease and other cognitive disorders Unit, Neurology Service, Hospital Clínic de Barcelona, FRCBIDIBAPS, Barcelona, Spain. Tel.: +34 932275785; E-mail: rsanchez@clinic.cat; ORCID: 0000-0001-7750-896X.

Abstract: We analyzed Lewy body (LB) pathology in 18 autosomal dominant Alzheimer’s disease (ADAD) brains via immunohistochemistry. Real-time quaking induced conversion was used to detect misfolded α-synuclein (α-syn) in 18 living ADAD cerebrospinal fluid (CSF) samples. Concomitant LB pathology was present in 44% ADAD brains. Only 6% CSF samples were positive for misfolded α-syn. In an additional AD sample, all patients with confirmed LB presented misfolded α-syn in postmortem CSF regardless of the LB staging. In conclusion, misfolded α-syn in CSF was scarce in symptomatic living ADAD individuals, in contrast to postmortem brain tissue. These results suggest late appearance of LB pathology in ADAD.

Keywords: α-Synuclein, autosomal dominant Alzheimer’s disease, Lewy body pathology, real-time quaking induced conversion

DOI: 10.3233/JAD-230919

Journal: Journal of Alzheimer's Disease, vol. 97, no. 3, pp. 1091-1096, 2024