Association of APOE epsilon 4 and Plasma p-tau181 with Preclinical Alzheimer's Disease and Longitudinal Change in Hippocampus Function

• 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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

Alzheimer's disease

APOE

fMRI

hippocampus

longitudinal

magnetic

resonance imaging

p-taul 81

phosphorylated tau

population-based

clinical diagnostic-criteria

resting-state connectivity

vascular

dementia

cortical plasticity

tau

risk

prediction

patterns

carriers

blood

Neurosciences & Neurology

Publication and Content Type

ref (subject category)

art (subject category)