tetracycline and Dementia

Conditional expression systems for 4-repeat wild-type (WT) tau or the corresponding mutants V337M and R406W were established in human neuroglioma H4 cells to study the effect of tau mutations on the physicochemical properties of tau, and to develop a cellular model for the formation of filamentous tau characteristic of frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and Alzheimer's disease. Upon induction tau expression increased, reaching maximal levels at 5 to 7 days. WT tau was phosphorylated at amino acids T181, S202/T205, T231, and S396/S404. The R406W mutation decreased tau phosphorylation at each of these sites as did the V337M mutation except for S396/S404 sites that increased. Most tau in postnuclear cell lysates was recovered in the supernatant fraction after centrifugation at 200,000 x g. The amount of tau in the pellet fraction increased more in mutant transfectants compared to WT when the induction was extended beyond 5 days. This particulate tau could be partially extracted with salt, Triton X-100, or sarkosyl. Of the transfectants, R406W had the highest proportion of sarkosyl-insoluble tau by day 7. This insoluble fraction was thioflavin S-positive and contained 15- to 5-nm-wide filaments with tau immunoreactivities. The R406W filaments were more abundant than those detected in similar preparations from WT or V337M transfectants. At the light microscopy level, most tau was found with microtubules, or diffusely distributed in the cytoplasm, but none of this appeared thioflavin S-positive. The results suggest that conditional tau transfectants are in a pretangle stage making them an attractive model system for studying intracellular tangle accumulation and for testing potential therapeutic agents as inhibitors for tau aggregation.

Topics: Chromosomes, Human, Pair 17; Dementia; Gene Expression Regulation; Glioma; Humans; Immunoblotting; Immunohistochemistry; Inclusion Bodies; Kinetics; Microscopy, Fluorescence; Microtubule-Associated Proteins; Mutation; Parkinson Disease; Phosphorylation; tau Proteins; Tetracycline; Transfection; Tumor Cells, Cultured

We report the case of a patient in the Psychiatric Department who complained of progressive impairment of cerebral functions consistent with dementia, diarrhea and fecal incontinence in the last few months. His medical history included a Billroth II gastrectomy for gastric ulcer. Biochemical tests detected cobalamin deficiency, without megaloblastic anemia, and an abnormal Schilling test that was not due to intrinsic factor deficiency. Once other causes of cobalamin deficiency were ruled out, we considered it as a deficiency disease due to blind loop syndrome. Treatment with parenteral vitamin B complex and long term oral antibiotic therapy allowed the complete and permanent resolution of neurologic and digestive symptoms. We consider this case to be interesting because it shows the existence of curable dementias and the usefulness of taking into account bacterial overgrowth, usually underestimated, as an entity that can produce a variety of disorders.

Topics: Administration, Oral; Anastomosis, Surgical; Anti-Bacterial Agents; Blind Loop Syndrome; Dementia; Gastrectomy; Humans; Jejunum; Male; Middle Aged; Tetracycline; Vitamin B 12; Vitamin B 12 Deficiency

Four patients with Whipple's disease which had responded to antibiotic therapy, later developed neurologic disease identical to that seen in patients with Whipple's disease who died without treatment. Dementia, myoclonus, ataxia, and supranuclear ophthalmoplegia were the main neurologic features. Restarting antibiotics has been followed by stabilization of disease in all four. Two have improved. In three, the previously diagnosed and treated Whipple's disease was not considered as a possible cause of the neurologic disease until the symptoms and signs were far advanced. It is advisable to periodically evaluate all patients with Whipple's disease, even after successful treatment. Signs of neurologic disease should be considered a possible recurrence of Whipple's disease and antibiotics restarted.

Topics: Adult; Anti-Bacterial Agents; Dementia; Female; Humans; Male; Memory Disorders; Middle Aged; Nervous System Diseases; Penicillins; Tetracycline; Whipple Disease

Topics: Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Dementia; Humans; Mental Disorders; Mentally Ill Persons; Oxytetracycline; Psychotic Disorders; Tetracycline