Association of Neurogranin and BACE1 With Clinical Cognitive Decline in Individuals With Subjective Cognitive Decline.
Humans
Aspartic Acid Endopeptidases
/ cerebrospinal fluid
Amyloid Precursor Protein Secretases
/ cerebrospinal fluid
Female
Male
Cognitive Dysfunction
/ cerebrospinal fluid
Aged
Neurogranin
/ cerebrospinal fluid
Disease Progression
Biomarkers
/ cerebrospinal fluid
Longitudinal Studies
Middle Aged
Aged, 80 and over
Journal
Neurology
ISSN: 1526-632X
Titre abrégé: Neurology
Pays: United States
ID NLM: 0401060
Informations de publication
Date de publication:
22 Oct 2024
22 Oct 2024
Historique:
medline:
20
9
2024
pubmed:
20
9
2024
entrez:
20
9
2024
Statut:
ppublish
Résumé
CSF biomarkers have immense diagnostic and prognostic potential for Alzheimer disease (AD). However, AD is still diagnosed relatively late in the disease process, sometimes even years after the initial manifestation of cognitive symptoms. Thus, further identification of biomarkers is required to detect related pathology in the preclinical stage and predict cognitive decline. Our study aimed to assess the association of neurogranin and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) with cognitive decline in individuals with subjective cognitive decline (SCD). We enrolled participants with available neurogranin and BACE1 measurements in CSF from the DELCODE (DZNE-Longitudinal Cognitive Impairment and Dementia, Germany) cohort. The longitudinal change of Preclinical Alzheimer's Cognitive Composite score was assessed as the primary outcome in participants with SCD and controls. The secondary outcome was defined as conversion of SCD to mild cognitive impairment (MCI) during follow-up. Levels of neurogranin, BACE1, and neurogranin/BACE1 ratio across groups were compared by analysis of covariance after adjustment for demographics. The linear mixed-effects model and Cox regression analysis were applied to evaluate their association with cognitive decline and progression of SCD to MCI, respectively. A total of 530 participants (mean age: 70.76 ± 6.01 years, 48.7% female) were analyzed in the study. The rate of cognitive decline was faster in individuals with SCD with higher neurogranin and neurogranin/BACE1 ratio (β = -0.138, SE = 0.065, Our findings suggest that CSF neurogranin and BACE1 begin to change in the preclinical stage of AD and they are associated with clinical progression in individuals with SCD.
Sections du résumé
BACKGROUND AND OBJECTIVES
OBJECTIVE
CSF biomarkers have immense diagnostic and prognostic potential for Alzheimer disease (AD). However, AD is still diagnosed relatively late in the disease process, sometimes even years after the initial manifestation of cognitive symptoms. Thus, further identification of biomarkers is required to detect related pathology in the preclinical stage and predict cognitive decline. Our study aimed to assess the association of neurogranin and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) with cognitive decline in individuals with subjective cognitive decline (SCD).
METHODS
METHODS
We enrolled participants with available neurogranin and BACE1 measurements in CSF from the DELCODE (DZNE-Longitudinal Cognitive Impairment and Dementia, Germany) cohort. The longitudinal change of Preclinical Alzheimer's Cognitive Composite score was assessed as the primary outcome in participants with SCD and controls. The secondary outcome was defined as conversion of SCD to mild cognitive impairment (MCI) during follow-up. Levels of neurogranin, BACE1, and neurogranin/BACE1 ratio across groups were compared by analysis of covariance after adjustment for demographics. The linear mixed-effects model and Cox regression analysis were applied to evaluate their association with cognitive decline and progression of SCD to MCI, respectively.
RESULTS
RESULTS
A total of 530 participants (mean age: 70.76 ± 6.01 years, 48.7% female) were analyzed in the study. The rate of cognitive decline was faster in individuals with SCD with higher neurogranin and neurogranin/BACE1 ratio (β = -0.138, SE = 0.065,
DISCUSSION
CONCLUSIONS
Our findings suggest that CSF neurogranin and BACE1 begin to change in the preclinical stage of AD and they are associated with clinical progression in individuals with SCD.
Identifiants
pubmed: 39303184
doi: 10.1212/WNL.0000000000209806
doi:
Substances chimiques
Aspartic Acid Endopeptidases
EC 3.4.23.-
Amyloid Precursor Protein Secretases
EC 3.4.-
Neurogranin
132654-77-4
BACE1 protein, human
EC 3.4.23.46
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM