Elevated CSF GAP-43 is associated with accelerated tau accumulation and spread in Alzheimer's disease.

In Alzheimer's disease, amyloid-beta (Aß) triggers the trans-synaptic spread of tau pathology, and aberrant synaptic activity has been shown to promote tau spreading. Aß induces aberrant synaptic activity, manifesting in increases in the presynaptic growth-associated protein 43 (GAP-43), which is closely involved in synaptic activity and plasticity. We therefore tested whether Aß-related GAP-43 increases, as a marker of synaptic changes, drive tau spreading in 93 patients across the aging and Alzheimer's spectrum with available CSF GAP-43, amyloid-PET and longitudinal tau-PET assessments. We found that (1) higher GAP-43 was associated with faster Aß-related tau accumulation, specifically in brain regions connected closest to subject-specific tau epicenters and (2) that higher GAP-43 strengthened the association between Aß and connectivity-associated tau spread. This suggests that GAP-43-related synaptic changes are linked to faster Aß-related tau spread across connected regions and that synapses could be key targets for preventing tau spreading in Alzheimer's disease.

Transorbital sonography and MRI reliability to assess optic nerve sheath diameter in idiopathic intracranial hypertension.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the performance of magnetic resonance imaging (MRI) in measuring the optic nerve sheath diameter (ONSD) compared to the established method transorbital sonography (TOS) in patients with idiopathic intracranial hypertension (IIH). METHODS: Twenty-three patients with IIH were prospectively included applying IIH diagnostic criteria. All patients received a lumbar puncture with assessment of the cerebrospinal fluid (CSF) opening pressure to assure the IIH diagnosis. Measurement of ONSD was performed 3 mm posterior to inner sclera surface in B-TOS by an expert examiner, while three independent neuroradiologists took measurements in axial T-weighted MRI examinations. The sella turcica with the pituitary gland (and potential presence of an empty sella) and the trigeminal cavity were also assessed on sagittal and transversal T1-weighted MRI images by one independent neuroradiologist. RESULTS: The means of ONSD between ultrasound and MRI measurements were 6.3 mm (standard deviation [SD] = 0.6 mm) and 6.2 mm (SD = 0.8 mm). The interrater reliability between three neuroradiologists showed a high interclass correlation coefficient (ICC) (confidence interval: .573 < ICC < .8; p < .001). In patients with an empty sella, the ONSD evaluated by MRI was 6.6 mm, while measuring 6.1 mm in patients without empty sella. No correlation between CSF opening pressure and ONSD was found. CONCLUSIONS: MRI can reliably measure ONSD and yields similar results compared to TOS in patients with IIH. Moreover, patients with empty sella showed significantly larger ONSD than patients without empty sella.