Investigating the Theranostic Potential of Graphene Quantum Dots in Alzheimer's Disease.

Alzheimer's disease (AD) is one of the leading causes of death worldwide, with no definitive diagnosis or known cure. The aggregation of Tau protein into neurofibrillary tangles (NFTs), which contain straight filaments (SFs) and paired helical filaments (PHFs), is a major hallmark of AD. Graphene quantum dots (GQDs) are a type of nanomaterial that combat many of the small-molecule therapeutic challenges in AD and have shown promise in similar pathologies. In this study, two sizes of GQDs, GQD7 and GQD28, were docked to various forms of Tau monomers, SFs, and PHFs. From the favorable docked poses, we simulated each system for at least 300 ns and calculated the free energies of binding. We observed a clear preference for GQD28 in the PHF6 (306VQIVYK311) pathological hexapeptide region of monomeric Tau, while GQD7 targeted both the PHF6 and PHF6* (275VQIINK280) pathological hexapeptide regions. In SFs, GQD28 had a high affinity for a binding site that is available in AD but not in other common tauopathies, while GQD7 behaved promiscuously. In PHFs, GQD28 interacted strongly near the protofibril interface at the putative disaggregation site for epigallocatechin-3-gallate, and GQD7 largely interacted with PHF6. Our analyses revealed several key GQD binding sites that may be used for detecting, preventing, and disassembling the Tau aggregates in AD.

Simultaneous new onset of neuromyelitis optica spectrum disorder in identical twins.

OBJECTIVE: To present a case of two identical twins presenting concurrently with symptoms and subsequent initial diagnosis of neuromyelitis optica spectrum disorder (NMOSD). METHODS: Clinical, laboratory and MRI findings for both twins were reviewed and presented here. RESULTS: Twin A presented with right eye pain and subsequent blurred vision in right eye. MRI of the brain and spine demonstrated pre-chiasmal right optic nerve enhancement and T2 hyperintense lesions in the spinal cord at T7 and T9 levels. Cerebrospinal fluid (CSF) analysis was remarkable for NMO/aquaporin-4 (AQP4) fluorescence-activated cell sorting (FACS) titre of 1:32 and a serum NMO/AQP4-IgG positive titre of 1:10 000. Twin B presented with diplopia. MRI of the brain and spine demonstrated T2 hyperintense lesions in the periventricular cerebral white matter, in the periaqueductal white matter of the pons, in the midbrain and the cervical spinal cord. Neurological examination findings revealed incomplete right trochlear palsy, rotatory nystagmus, an incomplete left internuclear ophthalmoplegia and hyper-reflexia. CSF analysis was remarkable for NMO/AQP4 FACS titre of 1:256 and a serum NMO-IgG positive titre of 1:10 000. Both twins responded well to intravenous steroid therapy. There was no adverse environmental exposure present. CONCLUSION: We present an interesting and rare case of identical twins presenting concurrently and for the first time with NMOSD.