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- Mielke, Michelle M, et al.
(författare)
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Cerebrospinal fluid sphingolipids, β-amyloid, and tau in adults at risk for Alzheimer's disease.
- 2014
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Ingår i: Neurobiology of aging. - : Elsevier BV. - 1558-1497 .- 0197-4580. ; 35:11, s. 2486-94
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Tidskriftsartikel (refereegranskat)abstract
- Cellular studies suggest sphingolipids may cause or accelerate amyloid-beta (Aβ) and tau pathology but invivo human studies are lacking. We determined cerebrospinal fluid levels of sphingolipids (ceramides and sphingomyelins), amyloid-beta (Aβ1-42, AβX-38, AβX-40, and AβX-42) and tau (T-tau and p-tau181) in 91 cognitively normal individuals, aged 36-69years, with a parental history of Alzheimer's disease. The 18-carbon acyl chain length ceramide species was associated with AβX-38 (r= 0.312, p= 0.003), AβX-40 (r= 0.327, p= 0.002), and T-tau (r= 0.313, p= 0.003) but not with AβX-42 (r= 0.171, p= 0.106) or p-tau (r= 0.086, p= 0.418). All sphingomyelin species correlated (most p < 0.001) with all Aβ species and T-tau; many also correlated with p-tau. Results remained in regression models after controlling for age and APOE genotype. These results suggest invivo relationships between cerebrospinal fluid ceramides and sphingomyelins and Aβ and tau levels in cognitively normal individuals at increased risk for Alzheimer's disease, indicating these sphingolipids may be associated with early pathogenesis.
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| 2. |
- Mielke, Michelle M., et al.
(författare)
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The 32-year relationship between cholesterol and dementia from midlife to late life.
- 2010
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Ingår i: Neurology. - 0028-3878. ; 75:21, s. 1888-95
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cellular and animal studies suggest that hypercholesterolemia contributes to Alzheimer disease (AD). However, the relationship between cholesterol and dementia at the population level is less clear and may vary over the lifespan. Methods: The Prospective Population Study of Women, consisting of 1,462 women without dementia aged 38–60 years, was initiated in 1968–1969 in Gothenburg, Sweden. Follow-ups were conducted in 1974–1975, 1980–1981, 1992–1993, and 2000–2001. All-cause dementia was diagnosed according to DSM-III-R criteria and AD according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria. Cox proportional hazards regression examined baseline, time-dependent, and change in cholesterol levels in relation to incident dementia and AD among all participants. Analyses were repeated among participants who survived to the age of 70 years or older and participated in the 2000–2001 examination. Results: Higher cholesterol level in 1968 was not associated with an increased risk of AD (highest vs lowest quartile: hazard ratio [HR] 2.82, 95% confidence interval [CI] 0.94–8.43) among those who survived to and participated in the 2000–2001 examination. While there was no association between cholesterol level and dementia when considering all participants over 32 years, a time-dependent decrease in cholesterol over the follow-up was associated with an increased risk of dementia (HR 2.35, 95% CI 1.22–4.58). Conclusion: These data suggest that midlife cholesterol level is not associated with an increased risk of AD. However, there may be a slight risk among those surviving to an age at risk for dementia. Declining cholesterol levels from midlife to late life may better predict AD risk than levels obtained at one timepoint prior to dementia onset. Analytic strategies examining this and other risk factors across the lifespan may affect interpretation of results.
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