We report two cases of superficial siderosis (SS) of the central nervous system (CNS), which is caused by chronic haemorrhaging into the subarachnoid space with haemosiderin deposition in the superficial portion of the CNS. Patient 1 had fluid collection in the spinal canal, which was reported as the source of the chronic bleeding. Patient 2 was bleeding from thickened dura at the level of the sacral vertebrae. Both of the patients had xanthochromic cerebrospinal fluid. We surgically repaired the sources of bleeding. Subsequently the cerebrospinal fluid (CSF) cleared and their symptoms were not aggravated for about 1 year. We measured several CSF markers of SS before and after surgery. Total tau protein (CSF-t-tau), phosphorylated tau protein (CSF-p-tau), iron (CSF-iron) and ferritin (CSF-ferritin) in the CSF were highly elevated at diagnosis. After surgery, the levels of CSF-t-tau and CSF-p-tau were markedly reduced while CSF-iron and CSF-ferritin had not decreased. It is suggested that CSF-t-tau and CSF-p-tau reflected the neural damage in SS and were useful to evaluate the effectiveness of SS therapies.

Alzheimer's disease (AD) is the most prevalent age‐related neurodegenerative disorder, mainly characterized by amyloid β (Aβ) accumulation in the brain. Numerous new agents are currently undergoing clinical trials as disease‐modifying therapies (DMTs) targeting Aβ. ALZ‐801 is a promising candidate DMT for AD, with a phase 3 trial of ALZ‐801 ongoing specifically for apolipoprotein E (APOE) ε4 homozygous patients with early‐stage AD. This study aimed to examine the effects of ALZ‐801 on Aβ assembly and explore its toxicological profile. Thioflavin T (ThT) assays and two imaging modalities—transmission electron microscopy (TEM) and high‐speed atomic force microscopy (HS‐AFM)—were used to evaluate ALZ‐801's effects on Aβ assembly. To assess the effect of ALZ‐801 on Aβ ₄₂ ‐induced cytotoxicity, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays and lactate dehydrogenase (LDH) assays were performed. ThT assays revealed increased lag time and decreased fluorescence in the presence of ALZ‐801, confirming inhibition of Aβ ₄₂ fibril formation, as confirmed by TEM. Real‐time observation using HS‐AFM revealed that ALZ‐801 inhibited the formation of Aβ ₄₂ fibril from low‐molecular‐weight (LMW)‐Aβ ₄₂ in the presence of Aβ ₄₂ seeds. HS‐AFM also revealed that globular aggregates from LMW‐Aβ ₄₂ were significantly larger with ALZ‐801, with few fibrils noted. MTT and LDH assays indicated that ALZ‐801 prevented LMW‐Aβ ₄₂ ‐induced cytotoxicity but did not reduce cytotoxicity induced by high‐molecular‐weight‐Aβ ₄₂ . ALZ‐801 can inhibit Aβ ₄₂ aggregation by preventing both nucleus formation and fibril elongation, while promoting large globular oligomer formation, and can significantly reduce LMW‐Aβ ₄₂ ‐induced cytotoxicity. These findings underscore the potential of ALZ‐801 as an effective DMT for APOE ε4 homozygous patients with AD.