A multicenter validation study on the diagnostic and prognostic value of CSF Neurogranin and BACE1
Xiao Wang, Silka Dawn Freiesleben, Luisa Sophie Schneider, Tatjana Gabelin, Lukas Preis, Josef Priller, Anja Schneider, Klaus Fließbach, Jens Wiltfang, Frank Jessen, Emrah Düzel, Katharina Buerger, Robert Perneczky, Stefan Teipel, Christoph Laske, Annika Spottke, Michael T. Heneka, Oliver Peters- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Cerebrospinal fluid (CSF) biomarkers have immense diagnostic and prognostic potential for Alzheimer disease (AD). Currently, AD is still mostly diagnosed relatively late in the disease process, sometimes even years after the initial manifestation of cognitive symptoms. Disease‐modifying treatments should be most effective in the earliest stages, before amyloid plaques and neurodegeneration become prevalent. Thus, further identification of biomarkers is required that can detect AD in the predementia stage. This study aimed to assess the clinical utility of synaptic proteins neurogranin and beta‐secretase 1 (BACE1) in the diagnosis and prognosis of AD.
Method
We enrolled 530 participants from DELCODE, a multicenter prospective cohort study, including healthy controls (HC), subjective cognitive decline (SCD) subjects, mild cognitive impairment (MCI) subjects, mild AD dementia and first‐degree relatives of AD patients. Based on amyloid and tau status, we divided the participants into four groups: A−T−; A−T+; A+T−; A+T+. Neurogranin and BACE1 levels across groups were assessed by ANCOVA after adjusted for age and sex. To test the correlation of the biomarkers to cognitive performance, we used linear mixed models to model baseline biomarker levels and 7 years longitudinal MMSE and PACC5 scores.
Result
Regardless of amyloid status, CSF neurogranin and BACE1 levels were significantly higher in T+ group compared with T‐ (all p < 0.0001). Furthermore, for participants with negative tau status, neurogranin and BACE1 levels were lower in A+ group compared with A‐ (both p < 0.0001). After adjusting for covariates (Age, Sex, Education, APOEε4), linear mixed‐effect models indicated that higher neurogranin predicts faster decline in MMSE (β = ‐0.14, p < 0.01) and PACC5 (β = ‐0.03, p < 0.05) over 7 years.
Conclusion
This study reveals that neurogranin and BACE1 could offer insight into identifying patients at early stages of AD and improve prediction of cognitive decline.