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- Salami, A., et al.
(författare)
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Association of APOE epsilon 4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function
- 2022
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Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 85:3, s. 1309-1320
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Apolipoprotein E (APOE) epsilon 4 allele has been linked to increased tau phosphorylation and tangle formation. APOE epsilon 4 carriers with elevated tau might be at the higher risk for Alzheimer's disease (AD) progression. Previous studies showed that tau pathology begins early in areas of the medial temporal lobe Similarly, APOE epsilon 4 carriers showed altered hippocampal functional integrity. However, it remains unknown whether the influence of elevated tau accumulation on hippocampal functional changes would be more pronounced for APOE epsilon 4 carriers. Objective: We related epsilon 4 carriage to levels of plasma phosphorylated tau (p-taul 81) up to 15 years prior to AD onset. Furthermore, elevated p-tau181 was explored in relation to longitudinal changes in hippocampal function and connectivity. Methods: Plasma p-taul 81 was analyzed in 142 clinically defined AD cases and 126 matched controls. The longitudinal analysis involved 87 non-demented individuals (from population-based study) with two waves of plasma samples and three waves of functional magnetic resonance imaging during rest and memory encoding. Results: Increased p-taul 81 was observed for both epsilon 4 carriers and non-carriers close to AD onset, but exclusively for epsilon 4 carriers in the early preclinical groups (7- and 13-years pre-AD). In epsilon 4 carriers, longitudinal p-taul 81 increase was paralleled by elevated local hippocampal connectivity at rest and subsequent reduction of hippocampus encoding-related activity. Conclusion: Our findings support an association of APOE epsilon 4 and p-tau181 with preclinical AD and hippocampus functioning.
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- Persson, J, et al.
(författare)
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Altered brain white-matter integrity in non-demented carriers of the APOE ε4 allele: A risk for Alzheimer’s disease.
- 2006
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 66:7, s. 1029-1033
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Tidskriftsartikel (refereegranskat)abstract
- Previous research has shown that polymorphisms of the apolipoprotein E (APOE) represent genetic risk factors for dementia and for cognitive impairment in the elderly. The neural mechanisms by which these genetic variations influence behavioral performance or clinical severity are not well understood. We used diffusion tensor imaging to investigate ultrastructural properties in brain white-matter to detect pathological processes that modify tissue integrity. Sixty participants were included in the study of which 30 were homozygous for the APOE ε3 allele, 10 were homozygous for the APOE ε4 allele, and 20 had the APOE ε34 allele combination. All individuals were non-demented, and the groups were matched on demographic variables and cognitive performance. The results showed a decline in fractional anisotropy, a marker for white-matter integrity, in the posterior corpus callosum of ε4 carriers compared to non-carriers. Additional sites of altered white-matter integrity included the medial temporal lobe. Conclusions: Although the mechanism underlying vulnerability of white matter tracts in APOE ε4 carriers is still unknown, our findings suggest that increased genetic risk for developing AD is associated with changes in microscopic white-matter integrity well before the onset of dementia.
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