Alpha-synuclein seeding activity in postmortem tissues from patients with diffuse and isolated Lewy bodies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F26%3A10001461" target="_blank" >RIV/00064190:_____/26:10001461 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1186/s40478-025-02195-6" target="_blank" >https://doi.org/10.1186/s40478-025-02195-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s40478-025-02195-6" target="_blank" >10.1186/s40478-025-02195-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Alpha-synuclein seeding activity in postmortem tissues from patients with diffuse and isolated Lewy bodies

Popis výsledku v původním jazyce

We have evaluated the diagnostic potential of the seeding amplification assay (SAA) in detecting alpha-synuclein seeding activity in postmortem brain and cerebrospinal fluid (CSF) samples from patients with primary and co-pathology alpha-synucleinopathies. Moreover, we investigated potential SAA positivity in control samples which may suggest unrecognized co-pathology. A total of 15 brain and 14 CSF samples with definite dementia with Lewy bodies (DLB, n = 6), Alzheimers disease with amygdala Lewy body (AD/ALB, n = 3), and patients with concomitant Creutzfeldt-Jakob disease and Lewy body pathology (CJD/LBP, n = 6) comorbidity were tested for alpha-synuclein seeding activity using SAA assay utilizing recombinant alpha-synuclein (WT) with N-terminal His-tag. Control samples consisted of other neurodegenerative diseases (n = 17 for brain and n = 18 for CSF samples) and healthy corneal donors (n = 17). The analysis of seeding activity in brain samples suggested 100% sensitivity and 91.2% specificity. Five out of 34 brain control samples gave a positive SAA outcome. However, upon reevaluation, two of these samples were reclassified as Alzheimers disease (AD) with synucleinopathy co-pathology. The analysis of CSF also suggested 100% sensitivity and 94.4% specificity, although dilution of some samples was necessary to decrease the effect of inhibitors. We report a good performance of the SAA not only in postmortem samples from primary synucleinopathies with advanced pathology, but also in co-pathology synucleinopathies with isolated Lewy bodies in the amygdala in AD cases. Our findings highlight the importance of careful diagnostic evaluation in AD patients, where co-existing synucleinopathy may otherwise go unrecognized.

Název v anglickém jazyce

Alpha-synuclein seeding activity in postmortem tissues from patients with diffuse and isolated Lewy bodies

Popis výsledku anglicky

We have evaluated the diagnostic potential of the seeding amplification assay (SAA) in detecting alpha-synuclein seeding activity in postmortem brain and cerebrospinal fluid (CSF) samples from patients with primary and co-pathology alpha-synucleinopathies. Moreover, we investigated potential SAA positivity in control samples which may suggest unrecognized co-pathology. A total of 15 brain and 14 CSF samples with definite dementia with Lewy bodies (DLB, n = 6), Alzheimers disease with amygdala Lewy body (AD/ALB, n = 3), and patients with concomitant Creutzfeldt-Jakob disease and Lewy body pathology (CJD/LBP, n = 6) comorbidity were tested for alpha-synuclein seeding activity using SAA assay utilizing recombinant alpha-synuclein (WT) with N-terminal His-tag. Control samples consisted of other neurodegenerative diseases (n = 17 for brain and n = 18 for CSF samples) and healthy corneal donors (n = 17). The analysis of seeding activity in brain samples suggested 100% sensitivity and 91.2% specificity. Five out of 34 brain control samples gave a positive SAA outcome. However, upon reevaluation, two of these samples were reclassified as Alzheimers disease (AD) with synucleinopathy co-pathology. The analysis of CSF also suggested 100% sensitivity and 94.4% specificity, although dilution of some samples was necessary to decrease the effect of inhibitors. We report a good performance of the SAA not only in postmortem samples from primary synucleinopathies with advanced pathology, but also in co-pathology synucleinopathies with isolated Lewy bodies in the amygdala in AD cases. Our findings highlight the importance of careful diagnostic evaluation in AD patients, where co-existing synucleinopathy may otherwise go unrecognized.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/NU23-04-00173" target="_blank" >NU23-04-00173: Využití metody RT-QuIC pro zpřesnění diagnostiky neurodegenerativních onemocnění: Prospektivní a retrospektivní studie</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2026

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACTA NEUROPATHOLOGICA COMMUNICATIONS

ISSN

2051-5960

e-ISSN

—

Svazek periodika

14

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

14

Strana od-do

nestránkováno

Kód UT WoS článku

001656348000001

EID výsledku v databázi Scopus

2-s2.0-105026929460