Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function
| Autor: | Alireza Salami, Rolf Adolfsson, Micael Andersson, Kaj Blennow, Anders Lundquist, Annelie Nordin Adolfsson, Michael Schöll, Henrik Zetterberg, Lars Nyberg |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Male
Heterozygote longitudinal hippocampus Apolipoprotein E4 Prodromal Symptoms tau Proteins phosphorylated tau Hippocampus Alzheimer Disease Humans magnetic resonance imaging Longitudinal Studies Phosphorylation Aged Aged 80 and over p-tau181 General Neuroscience fMRI Neurosciences General Medicine Magnetic Resonance Imaging population-based Psychiatry and Mental health Clinical Psychology Female Geriatrics and Gerontology Alzheimer’s disease APOE Neurovetenskaper |
| Popis: | Background: The Apolipoprotein E (APOE) ɛ4 allele has been linked to increased tau phosphorylation and tangle formation. APOE ɛ4 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 ɛ4 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 ɛ4 carriers. Objective: We related ɛ4 carriage to levels of plasma phosphorylated tau (p-tau181) 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-tau181 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-tau181 was observed for both ɛ4 carriers and non-carriers close to AD onset, but exclusively for ɛ4 carriers in the early preclinical groups (7- and 13-years pre-AD). In ɛ4 carriers, longitudinal p-tau181 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 ɛ4 and p-tau181 with preclinical AD and hippocampus functioning. |
| Databáze: | OpenAIRE |
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