Novel APP K724M mutation causes Chinese early-onset familial Alzheimer's disease and increases amyloid-ß42 to amyloid-ß40 ratio.

Alzheimer's disease (AD) is the most common neurodegenerative disorder among the elderly individuals. Although there are several million cases of AD estimated in China with the most population in the world, no Chinese early-onset familial AD caused by new APP gene mutation has ever been reported. Here, we first described a Chinese family with early-onset AD that was inherited in autosomal dominant manner, and the age of onset was 46.6 ± 7.7 years (n = 5; range, 40-58 years). By using genetic analysis of 3 collected patients' DNA samples, we identified a heterozygous APP gene mutation (g.275363A>T, K724M according to APP770). Finally, when APP695 with K724M mutation was ectopically expressed in HEK293 cell, the ratio of amyloid-ß42 to amyloid-ß40 was 2.23-fold higher than that of wild-type control. Together, our data suggest that APP K724M gene mutation may contribute to the cause of this Chinese early-onset familial AD.

[Age features of pure leukoaraiosis in non-demented outpatients].

OBJECTIVE: To investigate the aging features of pure leukoaraiosis (LA) in non-demented outpatients. METHODS: The outpatients with age older than 40 years, without taking cholesterol lowering and B vitamin medications and with mini-mental state examination more than 24 scores were selected from July 2008 to December. 2009 in Beijing Tiantan Hospital. LA was defined with MRI. Patients were classified into two groups i.e. LA group consisting of 138 patients with leukoaraiosis but without lacunar lesions and cortical infarcts and a control group consisting of 124 patients without any lesion in brain. Age and other vascular risk factors were also investigated. RESULTS: Age of the patients in the LA group was significantly higher than that in the control group (P<0.001). Multivariable logistic regression analysis showed that age was independently associated with pure LA (OR 1.080, 95%CI 1.042-1.120), after adjusting sex, vascular risk factors and presence of atherosclerosis in cervical arteries. If age-stratification was further considered, logistic regression analysis showed that OR (95%CI) for LA was 2.693 (95%CI 1.103-6.575) in a 60-69 year group and 13.527 (95%CI 3.319-55.131) in a ≥70 year group as compared with a 40-49 year group. CONCLUSION: Age is a determining risk factor for pure LA and patients with age older than 60 years are at high risk of LA.

[Neuropsychiatric symptoms in dementia and elderly people in the community: results from the Beijing Dementia Cooperative Study].

OBJECTIVE: To determine the prevalence of neuropsychiatric symptoms in dementia and normal elderly people living in the Chinese community of Beijing. METHODS: A cross-sectional study derived from the Beijing Dementia Cooperative Study was carried out a population survey was carried out on a total of 1540 participants aged 65 years and older living in Beijing city and rural areas. All the individuals and 373 demented elderly people completed a series of neuropsychological examination and the Neuropsychiatric Inventory (NPI). RESULTS: Among the dementia participants, 49.33% had exhibited neuropsychiatric symptoms (35.66% rated as clinically significant), in which 80.4% reported 2 or more disturbances, with depression (23.86%), apathy (21.72%) and anxiety (20.38%) being most common. Of the 1540 normal individuals, 18.25% of them exhibited neuropsychiatric symptoms (6.49% rated as clinically significant), in which 53% reported 2 or more disturbances, with sleepless (10%), depression (8.9%) and anxiety (6.97%) being the most common. CONCLUSION: To our knowledge, this was the first multi-center study on neuropsychiatric disturbances in dementia and cognitive normal elderly people. Neuropsychiatric symptoms occurred mainly in persons with dementia and of clinical severity. Though the neuropsychiatric disturbances reported in cognitive normal individuals were lower and less serious compared to dementia, they should not be neglected. These finding suggested that a screening programme focusing on identifying these symptoms should be included in the physician's diagnostic tools for dementia.