Neurosin, a novel type of trypsin-like serine protease, has been shown to be preferentially expressed in human brain by northern blotting. We examined neurosin immunolabeling in the brains of neurologically normal persons and patients with Alzheimer's disease (AD) and with Parkinson's disease. We also identified the expression of the mRNA for neurosin by in situ hybridization histochemistry and reverse transcription-polymerase chain reaction (RT-PCR).The neurosin antibody stained all of the nuclei of various cell types. In neurons, there was also staining of neuronal cytoplasm, nucleoli and their processes. In AD, staining of neurons with processes was rare in the damaged areas. Some senile plaques, extracellular tangles and Lewy bodies were also positive for neurosin. Expression of the mRNA for neurosin was seen in neurons in the gray matter, and in microglial cells in the white matter. In AD, the intensity of the signal for neurosin mRNA in the gray matter was decreased compared with normal control brains. The relative levels of neurosin mRNA in AD brains, measured by RT-PCR, were lower than those in controls. These results suggest that in human brain neurosin plays various physiological roles, and that in AD this molecule, like other serine proteases, may have a role in the degradation of such substances as b-amyloid protein.

No abstract

Several chemicals inhibit the accumulation of abnormal prion proteins in vitro. We administered one, the antimalarial agent quinacrine, to three patients with sporadic Creutzfeldt-Jakob disease (CJD) and to one with iatrogenic CJD. Quinacrine at 300 mg/day was given enterally for 3 months. Within 2 weeks of administration, the arousal level of the patient with akinetic mutism improved. The other 3 patients, insensible before treatment, had integrative responses such as eye contact or voluntary movement in response to verbal and/or visual stimuli restored. Clinical improvement was transient, lasting 1–2 months during treatment. Quinacrine was well tolerated, except for liver dysfunction and yellowish pigmentation. Although its antiprion activity in the human brain has yet to be proved, these modest effects of quinacrine suggest the possibility of using chemical intervention against prion diseases.

To investigate whether ataxia in Miller Fisher syndrome (MFS) is caused by loss of proprioception or cerebellar dysfunction, we studied the power spectrum peak of the body sway frequency in 10 MFS patients, and compared the results with those of patients with cerebellar or sensory ataxia. The cerebellar patients had a peak at 2.4 Hz, whereas sensory ataxia patients had a 1‐Hz peak. Nine of the MFS patients had a distinct 1‐Hz peak. Clinical sensory loss or abnormal sensory nerve potentials were present in only 3 patients, whereas soleus H‐reflexes were absent in all the MFS patients. MFS patients have dysfunction of the proprioceptive afferent system, and the special sensory ataxia may be caused by the selective involvement of muscle spindle afferents. Ann Neurol 1999;45:533–536

Using MRI, we investigated the morphology and blood-nerve barrier function of the peripheral nerve trunk in 10 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Eight patients had a focal demyelinative segment in the median or ulnar nerve trunk that was defined by conduction block or abnormal temporal dispersion over a short distance. These demyelinative foci showed nerve enlargement with high signal intensity on proton or T2-weighted images. In four patients with progressive illness or relapse, the enlarged segment showed gadolinium enhancement that disappeared during remission induced by immune therapies. The other four were in the steady phase and showed no gadolinium enhancement of the enlarged nerves. The two patients who showed conduction slowing, but no focal demyelinative focus, had neither nerve enlargement nor gadolinium enhancement. In CIDP, focal conduction abnormalities correlate well with anatomic changes that suggest intermittent, repeated inflammation associated with the breakdown of the blood-nerve barrier.