No genetic association between Fyn kinase gene polymorphisms (-93A/G, IVS10+37T/C and Ex12+894T/G) and Japanese sporadic Alzheimer's disease.

Several groups have reported that abnormal phosphorylation of tau by Fyn, a protein-tyrosine kinase, may play a role in the neuropathogenesis of Alzheimer's disease (AD). In the present study, three common Japanese polymorphisms of the Fyn gene (-93A/G in the 5'-flanking region, IVS10+37T/C in intron 10 and Ex12+894T/G in the 3'-untranslated region) were studied in 127 healthy controls and 182 sporadic AD cases using a polymerase chain reaction restriction fragment length polymorphism method. A comparison of the allelic and genotypic frequencies of these polymorphisms between controls and sporadic AD cases failed to show any significant difference. These results suggest that the Fyn polymorphisms (-93A/G, IVS10+37T/C and Ex12+894T/G) investigated here have no genetic association with sporadic AD.

[The Japanese version of RBANS (Repeatable Battery for the Assessment of Neuropsychological Status)].

In Japan, neuropsychological assessment of dementing illnesses has been done mainly using Mini-Mental State Examination (MMSE) and a revised version of Hasegawa Dementia Scale (HDS-R). However, because of a lack of appropriately designed test domains, early detection of senile dementia and/or cognitive impairment is hardly possible, even if using these batteries. This paper is to introduce a Japanese Version of RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) which was originally developed by Randolph and revised by us. The entire battery of Japanese Version RBANS took less than 30 minutes to administer, and yielded scaled scores for five cognitive domains such as immediate memory, visuospatial/constructional ability, language, attention, and delayed memory. On RBANS, abnormal cognitive decline in the older adult was much easily detected, being compared to MMSE and HDS-R: 52 normal volunteer subjects ranging from 24 to 80 years old showed a significant (p < 0.05 on t test) impairment of delayed and immediate memories due to ageing. The aged (60-79) subjects with average scores of MMSE and HDS-R being over 25, significantly showed impairment of both immediate memory (list and story learnings) and delayed memory (list, story and figure recalls). The present data suggest that the Japanese Version RBANS is useful for both detecting and characterizing early dementia, and should be widely utilized for a neuropsychological screening battery in the clinical practice throughout Japan.

Effect of IL-6 polymorphism on risk of Alzheimer disease: genotype-phenotype association study in Japanese cases.

Interleukin-6 (IL-6), an inflammatory cytokine might be involved in the pathophysiology of Alzheimer disease (AD); several studies have reported that the "C allele of IL-6 variable number of tandem repeat polymorphism" (IL-6vntr) delayed initial onset of AD and also decreased its risk per se. Another polymorphism, G/C allele of IL-6 gene promoter region (IL-6prom), is also a candidate because it has an influence on the regulation of plasma IL-6 concentration. We examined these IL-6 polymorphisms in 128 Japanese AD cases and 83 control cases using a PCR-RFLP method. The results showed the frequency of the IL-6prom G allele was significantly increased in AD, although IL-6vntr polymorphism was not. Plasma IL-6 concentration of the AD cases was also significantly higher than that of the control cases. Moreover, the IL-6prom G allele-positive AD patients showed a tendency to have higher IL-6 concentration in the AD group. These findings suggest that the IL-6prom G allele which may affect plasma IL-6 concentration might be a risk factor for sporadic AD in Japanese.

The effect of IL4 +33C/T polymorphism on risk of Japanese sporadic Alzheimer's disease.

Interleukin-4 (IL4) is an anti-inflammatory cytokine that may play a role in the inflammation pathology observed surrounding senile plaques, and may also associate with Alzheimer's disease (AD) pathogenesis. Recently, it has been reported that a single nucleotide polymorphism in the IL4 gene promoter region, IL4 +33C/T polymorphism, associates with its phenotype. It was thought that the IL4 +33C/T polymorphism causing high IL4 production may reduce the risk for AD. In the present study, therefore, we investigated this mutation in 108 healthy controls and in 178 sporadic AD cases by the polymerase chain reaction restriction fragment length polymorphism method in a Japanese AD population. Allelic frequencies with +33C/T polymorphism in the gene were 35.6 and 32.6% in the control and AD groups, respectively. Our results failed to demonstrate an association between this polymorphism and Japanese sporadic AD. We also tested whether the IL4 functional variants were regulated by this polymorphism in a portion of the subjects (16 AD cases and 13 control cases). We could not find any relationship between the IL4 +33C/T polymorphism and plasma IL4 concentration.