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Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Aging Research Center, Karolinska Institute, Stockholm, Sweden.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.ORCID iD: 0000-0001-9785-8473
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).ORCID iD: 0000-0003-4743-6365
Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
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2022 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 85, no 3, p. 1309-1320Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
IOS Press, 2022. Vol. 85, no 3, p. 1309-1320
Keywords [en]
Alzheimer’s disease, APOE, fMRI, hippocampus, longitudinal, magnetic resonance imaging, p-tau181, phosphorylated tau, population-based
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Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-192513DOI: 10.3233/JAD-210673ISI: 000752449800030PubMedID: 34924376Scopus ID: 2-s2.0-85124174700OAI: oai:DiVA.org:umu-192513DiVA, id: diva2:1639854
Available from: 2022-02-22 Created: 2022-02-22 Last updated: 2024-04-08Bibliographically approved

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Salami, AlirezaAdolfsson, RolfAndersson, MicaelLundquist, AndersNordin Adolfsson, AnnelieNyberg, Lars

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Salami, AlirezaAdolfsson, RolfAndersson, MicaelLundquist, AndersNordin Adolfsson, AnnelieNyberg, Lars
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Department of Integrative Medical Biology (IMB)Umeå Centre for Functional Brain Imaging (UFBI)Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)PsychiatryStatisticsDiagnostic Radiology
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