Cerebrospinal fluid surfactant protein-G in neurodegenerative dementia: A comparative study with idiopathic normal-pressure hydrocephalus

Background Surfactant protein G (SP-G) is a recently characterized protein potentially involved in cerebrospinal fluid (CSF) dynamics. Its role in human neurodegenerative dementia remains unknown. Objective To investigate the potential clinical relevance of CSF SP-G levels in neurodegenerative dementia (ND; including Alzheimer's disease [AD] and frontotemporal dementia [FTD]), idiopathic normal-pressure hydrocephalus (iNPH), vascular dementia (VaD), and clinical controls (CTR). Methods CSF SP-G levels were quantified in 94 individuals: 35 with ND (11 AD + 24 FTD), 19 with iNPH, 13 with VaD, and 27 CTR. Group differences were analyzed using ANOVA with post hoc tests. ANCOVA was performed to adjust for age. Results CSF SP-G levels differed significantly among groups in the primary analysis (ANOVA: F(3,90) = 3.862, p = 0.012), with higher levels in iNPH compared with ND (p = 0.012) and CTR (p = 0.026). No significant differences were observed between ND, VaD, and CTR groups. After adjustment for age, the group effect was no longer significant (F(3,89) = 2.253, p = 0.088). Conclusions This is the first study to investigate CSF SP-G levels in neurodegenerative dementia. Our findings suggest that SP-G is more closely related to altered CSF physiology in iNPH than to neurodegenerative pathology, although the influence of age indicates that these observations should be interpreted with caution. SP-G may represent a candidate marker of CSF homeostasis and fluid dynamics. Larger, age-matched studies integrating SP-G with established CSF biomarkers and neuroimaging are needed to clarify its diagnostic and pathophysiological significance.