Titre :

Clarifying the association of CSF Aβ, tau, BACE1, and neurogranin with AT(N) stages in Alzheimer disease

Auteur(s) :

Lehmann, S. [Auteur]
Université de Montpellier [UM]
Schraen, Susanna [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Buee, Luc [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Vidal, J. S. [Auteur]
Groupe hospitalier Broca
Delaby, C. [Auteur]
Hospital de la Santa Creu i Sant Pau
Université de Montpellier [UM]
Hirtz, C. [Auteur]
Université de Montpellier [UM]
Blanc, F. [Auteur]
Université de Strasbourg [UNISTRA]
Paquet, C. [Auteur]
Université Paris Cité [UPCité]
Allinquant, B. [Auteur]
Université Paris Cité [UPCité]
Bombois, Stephanie [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Gabelle, A. [Auteur]
Université de Montpellier [UM]
Hanon, O. [Auteur]
Université Paris Cité [UPCité]

Titre de la revue :

Mol. Neurodegener.

Nom court de la revue :

Mol. Neurodegener.

Numéro :

19

Pagination :

-

Date de publication :

2024-11-18

ISSN :

1750-1326

Mot(s)-clé(s) en anglais :

Alzheimer's disease
Amyloid
BACE1
Cerebrospinal fluid
Neurodegeneration
Neurogranin
Tau proteinopathy

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Background: Current AT(N) stratification for Alzheimer's disease (AD) accounts for complex combinations of amyloid (A), tau proteinopathy (T) and neurodegeneration (N) signatures. Understanding the transition between these ...
Lire la suite >Background: Current AT(N) stratification for Alzheimer's disease (AD) accounts for complex combinations of amyloid (A), tau proteinopathy (T) and neurodegeneration (N) signatures. Understanding the transition between these different stages is a major challenge, especially in view of the recent development of disease modifying therapy. Methods: This is an observational study, CSF levels of Tau, pTau181, pTau217, Aβ38/40/42, sAPPα/β, BACE1 and neurogranin were measured in the BALTAZAR cohort of cognitively impaired patients and in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Biomarkers levels were related to the AT(N) framework. (A) and (T) were defined in BALTAZAR with CSF Aβ42/40 ratio and pTau217 respectively, and in ADNI with amyloid and tau PET. (N) was defined using total CSF tau in both cohorts. Results: As expected, CSF Aβ42 decreased progressively with the AD continuum going from the A-T-N- to the A + T + N + profile. On the other hand, Tau and pTau181 increased progressively with the disease. The final transition from A + T + N- to A + T + N + led to a sharp increase in Aβ38, Aβ42 and sAPP levels. Synaptic CSF biomarkers BACE1 and neurogranin, were lowest in the initial A + T-N- stage and increased with T + and N + . CSF pTau181 and total tau were closely related in both cohorts. Conclusions: The early transition to an A + phenotype (A + T-N-) primarily impacts synaptic function. The appearance of T + and then N + is associated with a significant and progressive increase in pathological Alzheimer's disease biomarkers. Our main finding is that CSF pTau181 is an indicator of N + rather than T + , and that N + is associated with elevated levels of BACE1 protein and beta-amyloid peptides. This increase may potentially fuel the amyloid cascade in a positive feedback loop. Overall, our data provide further insights into understanding the interconnected pathological processes of amyloid, tau, and neurodegeneration underlying Alzheimer's disease.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Alzheimer et Tauopathies

Date de dépôt :

2024-11-19T22:01:50Z
2025-03-05T08:58:46Z
2025-03-05T09:36:39Z