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- van der Lee, S. J., et al.
(författare)
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A nonsynonymous mutation in PLCG2 reduces the risk of Alzheimer's disease, dementia with Lewy bodies and frontotemporal dementia, and increases the likelihood of longevity
- 2019
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 138:2, s. 237-250
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Tidskriftsartikel (refereegranskat)abstract
- The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). The role of PLCG2 in immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates with longevity. We studied the effect of the rs72824905-G on seven neurodegenerative diseases and longevity, using 53,627 patients, 3,516 long-lived individuals and 149,290 study-matched controls. We replicated the association of rs72824905-G with reduced AD risk and we found an association with reduced risk of dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We did not find evidence for an effect on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) risks, despite adequate sample sizes. Conversely, the rs72824905-G allele was associated with increased likelihood of longevity. By-proxy analyses in the UK Biobank supported the associations with both dementia and longevity. Concluding, rs72824905-G has a protective effect against multiple neurodegenerative diseases indicating shared aspects of disease etiology. Our findings merit studying the PLC gamma 2 pathway as drug-target.
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- Gustafson, D, et al.
(författare)
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An 18-year follow-up of overweight and risk of Alzheimer disease
- 2003
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Ingår i: Archives of Internal Medicine. - 0003-9926 .- 1538-3679. ; 163:13, s. 1524-1528
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Tidskriftsartikel (refereegranskat)abstract
- Background Overweight and obesity are epidemic in Western societies and constitute a major public health problem because of adverse effects on vascular health. Vascular factors may play a role in the development of a rapidly growing disease of late life, Alzheimer disease (AD). Using body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), we examined whether overweight is a risk factor for dementia and AD.Methods The relationship between BMI and dementia risk was investigated in a representative cohort of 392 nondemented Swedish adults who were followed up from age 70 to 88 years, with the use of neuropsychiatric, anthropometric, and other measurements. Multivariate Cox proportional hazards regression analyses included BMI, blood pressure, cardiovascular disease, cigarette smoking, socioeconomic status, and treatment for hypertension.Results: During the 18-year follow-up (4184.8 risk-years), 93 participants were diagnosed as having dementia. Women who developed dementia between ages 79 and 88 years were overweight, with a higher average BMI at age 70 years (27.7 vs 25.7; P = .007), 75 years (27.9 vs 25.0; P<.001), and 79 years (26.9 vs 25.1; P = .02) compared with nondemented women. A higher degree of overweight was observed in women who developed AD at 70 years (29.3; P = .009), 75 years (29.6; P<.001), and 79 years (28.2; P = .003) compared with nondemented women. For every 1.0 increase in BMI at age 70 years, AD risk increased by 36%. These associations were not found in men.Conclusions Overweight is epidemic in Western societies. Our data suggest that overweight at high ages is a risk factor for dementia, particularly AD, in women. This may have profound implications for dementia prevention.
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