Association of neurogranin and BACE1 with clinical cognitive decline in individuals with subjective cognitive decline

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Item Type:	Article
Title:	Association of neurogranin and BACE1 with clinical cognitive decline in individuals with subjective cognitive decline
Creators Name:	Wang, X., Freiesleben, S.D., Schneider, L.S., Preis, L., Priller, J., Spruth, E.J., Altenstein, S., Schneider, A., Fliessbach, K., Wiltfang, J., Hansen, N., Jessen, F., Rostamzadeh, A., Duzel, E., Glanz, W., Incesoy, E.I., Buerger, K., Janowitz, D., Ewers, M., Perneczky, R., Rauchmann, B.S., Teipel, S.J., Kilimann, I., Goerss, D., Laske, C., Munk, M.H.J., Spottke, A., Roy-Kluth, N., Heneka, M.T., Brosseron, F., Wagner, M., Wolfsgruber, S., Ramirez, A., Kleineidam, L., Stark, M. and Peters, O.
Abstract:	BACKGROUND AND OBJECTIVES: 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 ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1) with cognitive decline in individuals with subjective cognitive decline (SCD). 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: 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 (ß = -0.138, SE = 0.065, p = 0.037, and ß = -0.293, SE = 0.115, p = 0.013). Higher baseline neurogranin and neurogranin/BACE1 ratio were associated with an increased rate of conversion from SCD to MCI (hazard ratio [HR] 1.35 per SD, 95% CI 1.03-1.77, p = 0.028, and HR 1.53 per SD, 95% CI 1.13-2.07, p = 0.007). In addition, the impact of higher neurogranin levels on accelerating the rate of cognitive decline was more pronounced in the SCD group than in cognitively unimpaired controls (ß = -0.077, SE = 0.033, p = 0.020). DISCUSSION: 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.
Keywords:	Amyloid Precursor Protein Secretases, Aspartic Acid Endopeptidases, Biomarkers, Cognitive Dysfunction, Disease Progression, Longitudinal Studies
Source:	Neurology
ISSN:	0028-3878
Publisher:	Lippincott Williams & Wilkins
Volume:	103
Number:	8
Page Range:	e209806
Date:	22 October 2024
Official Publication:	https://doi.org/10.1212/wnl.0000000000209806
PubMed:	View item in PubMed

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