In patients with pemphigus vulgaris (PV), autoantibodies against desmoglein 3 (Dsg3) cause loss of cell–cell adhesion of keratinocytes in the basal and immediate suprabasal layers of stratified squamous epithelia. The pathology, at least partially, may depend on protease release from keratinocytes, but might also result from antibodies interfering with an adhesion function of Dsg3. However, a direct role of desmogleins in cell adhesion has not been shown. To test whether Dsg3 mediates adhesion, we genetically engineered mice with a targeted disruption of the DSG3 gene. DSG3 −/− mice had no DSG3 mRNA by RNase protection assay and no Dsg3 protein by immunofluorescence (IF) and immunoblots. These mice were normal at birth, but by 8–10 d weighed less than DSG3 +/− or +/+ littermates, and at around day 18 were grossly runted. We speculated that oral lesions (typical in PV patients) might be inhibiting food intake, causing this runting. Indeed, oropharyngeal biopsies showed erosions with histology typical of PV, including suprabasilar acantholysis and “tombstoning” of basal cells. EM showed separation of desmosomes. Traumatized skin also had crusting and suprabasilar acantholysis. Runted mice showed hair loss at weaning. The runting and hair loss phenotype of DSG3 −/− mice is identical to that of a previously reported mouse mutant, balding (bal). Breeding indicated that bal is coallelic with the targeted mutation. We also showed that bal mice lack Dsg3 by IF, have typical PV oral lesions, and have a DSG3 gene mutation. These results demonstrate the critical importance of Dsg3 for adhesion in deep stratified squamous epithelia and suggest that pemphigus autoantibodies might interfere directly with such a function.

Background: Several studies have reported that the prevalence of idiopathic normal-pressure hydrocephalus (iNPH) was between 0 and 5%. However, the precise prevalence in a community-based elderly population remains unclear. We investigated the prevalence of possible iNPH retrospectively using an age- and gender-stratified random sample database. Methods: Five hundred and sixty-seven participants were randomly selected from among the 1,654 members of the population aged 65 years and older in Tajiri, Japan, and 497 underwent MRI. We classified participants as having possible iNPH if they had: (1) ventricular enlargement, as shown by an Evans index of ≥0.3, with closing sulci at the high convexity with dilation of the sylvian fissure on MRI, (2) at least one of the iNPH clinical triad (gait disturbance, urinary incontinence and cognitive impairment), and (3) no identifiable potential secondary cause of hydrocephalus. Results: We found 7 participants who met the criteria mentioned above. Cognitive impairments were the most common symptoms (n = 6) followed by gait disturbances (n = 3); however, urinary incontinence was not observed. No full clinical triad was present in the patients and only 3 participants had 2 of the triad. Conclusions: We considered the prevalence of possible iNPH in elderly adults to be 1.4% (95% confidence interval = 0.6–2.9%).

Background: There have been no reports on the prevalence of dementia among the old-old people in Japan. Methods: We studied the old-old population in Kurihara, northern Japan. Analysis 1 of Participants 1 (n = 590) was performed to evaluate the prevalence of dementia and dementing diseases by intensive evaluation including MRI. Analysis 2 aimed to determine a good indicator for detecting 'suspected dementia condition' based on the Long-Term Care Insurance index. Analysis 3 of Participants 2 (n = 3915) aimed to estimate the prevalence of 'suspected dementia condition'. Results: In Analysis 1, 73 people (12.4%) were diagnosed with dementia. The most common cause was Alzheimer's disease with cerebrovascular disease. In Analysis 2, level I of the Impairment Level of Dementia was found to be a good indicator of 'suspected dementia condition'. In Analysis 3, the overall estimated prevalence of 'suspected dementia condition' was 23.6%. In men, the ratio increased gradually from 75 to 87 years old to about 20%, increased to 40% at the age of 88 and became stable thereafter. In contrast, in women, the ratio increased from 75 to 95+ years old, reaching about 70%. Conclusions: The prevalence was higher than that reported previously. There was a difference between the sexes: an 'age-related' increase occurred in men and an 'ageing-related' increase in women. Alzheimer's disease with cerebrovascular disease was the most common cause, which coincided with the previous findings of individuals aged 65 years and older; however, the ratio of mixed dementia was greater.

Prevalence, magnetic resonance imaging (MRI) findings, cognitive function and depression are four major aspects of vascular cognitive impairment no dementia (vascular CIND). We performed a community-based study to examine these using 497 community-residents aged 65 years or older. Vascular CIND was defined as a clinical dementia rating (CDR) 0.5 with cerebrovascular disease. Several neuropsychological tests were performed, including MMSE, Geriatric Depression Scale (GDS), and Trail Making Test (TMT). Cerebrovascular disease and white matter lesions were visually assessed using MRI. Prevalence of vascular CIND, localization of cerebrovascular disease, and the relationships amongst MRI findings, white matter lesions, cognitive impairment and depression were analyzed. The prevalence of vascular CIND was 8.5% amongst the total population, corresponding to the rate being 37.2% amongst the CDR 0.5 participants. Compared with the CDR 0, the CDR 0.5 group had more subjects with strategic cerebrovascular disease in the thalamus, etc. No effects of cerebrovascular disease on MMSE and GDS scores were found, but the CDR 0.5/strategic cerebrovascular disease group showed impaired TMT-B scores. In the CDR 0 group, only anterior periventricular hyperintensity was associated with TMT-A score independent of cerebrovascular disease. A vascular CIND population was identified, and executive dysfunction in this population is probably based on an impaired fronto-subcortical circuit.