CSF-G

Functional aspects of cerebrospinal fluid drainage through the cribriform plate.

Shanbhag Nagesh C NC, Jukkola Jari J, Kritsilis Marios M, Bèchet Nicholas B NB et al.

Cerebrospinal fluid (CSF) clearance is essential for maintaining brain homeostasis, yet the contribution of the nasal efflux pathway remains incompletely understood. Here, we combined dynamic contrast-enhanced magnetic resonance imaging, optical imaging, and anatomical studies across mice and pigs to characterize the dynamics, regulation, and conservation of nasal CSF drainage. We found that CSF rapidly exited the brain via the cribriform plate, especially during acute volume shifts, and that this route slowed down in aged mice when a small-molecular-weight tracer was used. By contrast, olfactory sensory neuron ablation and amyloid beta1-42 exposure impaired uptake of CSF into the nasal pathway. Notably, signal uptake in superficial cervical lymph nodes appeared distinct from meningeal lymphatic drainage, suggesting functional specialization. Our corroborating findings in pigs further solidify the nasal CSF efflux route as a dynamic, evolutionarily conserved, and potentially targetable pathway with relevance to neuroimmune interactions, aging, and neurodegeneration.

Effect of Eye Movement and Body Position on Optic Nerve Sheath Width.

Huyhn Duy D, Ohri Simran S, Garg Viraj V, Zehden Jason J et al.

Orbital cerebrospinal fluid (CSF) dynamics are poorly understood but are postulated to play a role in several optic nerve pathologies. This study aims to evaluate the effects of eye movement and body position on perioptic CSF clearance by optic nerve sheath width (ONSW) measurement. Healthy adult patients were recruited prospectively from an outpatient ophthalmology clinic at an academic center. B-mode ultrasound was used to measure optic nerve sheath width (ONSW) 3 mm posterior to the optic disc after 5 minutes of no eye movement (-EM) and 1 minute of eye movement (+EM) in three body positions: upright, supine, and prone. CSF clearance is the difference between ONSW +EM and -EM in each body position. Thirty-eight adults with healthy optic nerves were recruited. ONSW -EM were significantly wider than +EM in all three positions (P = 0.002, 0.024, 0.002). Body positioning only significantly affected ONSW -EM (P = 0.030), while +EM ONSW was not significantly different in any body position, indicating a baseline effect. Eye movement and body position significantly impact orbital CSF dynamics and ONSW. Prone positioning increased ONSW, highlighting the role of gravity dependence in perioptic CSF clearance. Identifying factors that impact CSF dynamics is imperative to understanding its part in optic nerve disease.

CSF Biomarker-Supported Alzheimer's Disease Presenting as Primary Progressive Aphasia With a Negative Amyloid PET: A Case Report.

Lee Hyoyoung H, Ha Sun Yeon SY, An Hyokyeong H, Lee Sung Eun SE et al.

Mediation of the Association Between APOE Genotype and Cognitive Change Through Alzheimer's Disease Biomarkers in Patients With Mild Cognitive Impairment.

Lee Sangjae S, Heo Min M, Kim Yeshin Y, Kim Seongheon S et al.

Apolipoprotein E (APOE) ε4 is associated with Alzheimer's disease risk and amyloid pathology, but whether cerebrospinal fluid (CSF) Alzheimer's disease biomarkers show statistical indirect effects in its association with longitudinal clinical worsening in mild cognitive impairment (MCI) remains unclear. We analyzed 397 participants with MCI from the Alzheimer's Disease Neuroimaging Initiative. The primary analysis used 36-month change in Clinical Dementia Rating-Sum of Boxes (CDR-SB) in the full cohort. APOE ε4 carrier status was the predictor, baseline CSF amyloid beta 1-42 (Aβ42) and phosphorylated tau 181 (p-tau181) were serial mediators, and age, sex, and education were covariates. Secondary analyses were stratified by amyloid status, and 12- and 24-month analyses and APOE ε4 allele-count models were exploratory and sensitivity analyses, respectively. Indirect effects were evaluated using 5,000 percentile bootstrap resamples. In the full cohort, the total effect of APOE ε4 on 36-month CDR-SB change was significant (estimate, 1.047; 95% bootstrap confidence interval [CI], 0.552 to 1.540), whereas the residual direct effect was not (0.097; 95% CI, -0.447 to 0.636). The Aβ42-specific indirect effect was significant (0.751; 95% CI, 0.474 to 1.035), while the p-tau181-specific (0.068; 95% CI, -0.007 to 0.167) and sequential Aβ42-to-p-tau181 indirect effects (0.131; 95% CI, -0.002 to 0.309) were not. Secondary and allele-count sensitivity analyses were directionally consistent. Lower CSF Aβ42 showed a significant statistical indirect association between APOE ε4 carrier status and 36-month clinical worsening in MCI. These observational findings do not establish a causal mediating mechanism.