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. 2018 Aug 6;8(2):277-289.
doi: 10.1159/000489847. eCollection 2018 May-Aug.

Neurogranin and BACE1 in CSF as Potential Biomarkers Differentiating Depression with Cognitive Deficits from Early Alzheimer's Disease: A Pilot Study

Carola G Schipke  1 , Ann De Vos  2 , Manuel Fuentes  3 , Dirk Jacobs  1 , Eugeen Vanmechelen  1 , Oliver Peters  3   4
Affiliations

Neurogranin and BACE1 in CSF as Potential Biomarkers Differentiating Depression with Cognitive Deficits from Early Alzheimer's Disease: A Pilot Study

Carola G Schipke et al. Dement Geriatr Cogn Dis Extra. .

Abstract

Background/aims: Major depressive disorder (MDD) can cooccur with early Alzheimer's disease (AD) or may cause memory problems independently of AD. Previous studies have suggested that the AD-related cerebrospinal fluid (CSF) biomarkers tau and Aβ(1-42) could help discriminate between early AD and depression unrelated to AD. Moreover, the postsynaptic protein neurogranin and presynaptic BACE1 have increasingly gained attention as potential new AD biomarkers, but they have not yet been investigated concerning depression.

Methods: Using ELISAs, we studied CSF neurogranin and BACE1 levels in patients with mild (n = 21) and moderate (n = 19) AD, as well as in MDD patients with (n = 20) and without (n = 20) cognitive deficits. The clinical examinations included analyses of t-tau, Aβ(1-42), and Aβ(1-40), besides neuropsychological tests and cranial magnetic resonance imaging. Depressive symptom severity was assessed using the Geriatric Depression Scale (GDS).

Results: Along with classic AD biomarkers, neurogranin and BACE1 CSF levels differed between moderate AD and MDD (p ≤ 0.01). MDD associated with cognitive deficits was distinguished from mild AD through the CSF neurogranin/BACE1 ratio (p < 0.05), which was strongly correlated with GDS scores (ρ = -0.656; p < 0.01).

Conclusion: The neurogranin/BACE1 ratio in CSF can distinguish between depression and AD among patients with similar cognitive deficits, along with the classic AD biomarkers. Further longitudinal studies are ongoing to identify which biomarkers have prognostic value.

Keywords: Alzheimer's disease; BACE1 protein; Cerebrospinal fluid; Depression; ELISA; Neurogranin.

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Figures

Fig. 1
Fig. 1
Scatter dot plots demonstrating CSF concentrations of neurogranin (a) and BACE1 (b) and the neurogranin/BACE1 ratio in CSF (c). Median levels are depicted as lines in each plot; bars represent the interquartile range. Statistically significant differences: * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. MDD/CogN, depression without cognitive deficits; MDD/CogD, depression with cognitive deficits; ADmild, mild Alzheimer's disease; ADmod, moderate Alzheimer's disease.
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