Entorhinal tau is associated with increased hippocampal activation and memory deficits in Alzheimer’s disease

Abstract

AbstractBackgroundTo date, it remains unclear how the hallmark pathological changes of Alzheimer’s disease (AD), amyloid plaques, and neurofibrillary tangles, affect neuronal activity and, consequently, cognition. In cognitively normal aging, it appears that tau accumulation may drive hippocampal hyperactivity, however, studies investigating this association in AD are sparse.MethodPatients with mild cognitive impairment (MCI) or mild dementia due to AD (n = 15) underwent positron emission tomography with the tracer [18F]‐AV‐1451, which binds to tau accumulation, and performed a visual item memory task during functional magnetic resonance imaging.ResultEntorhinal tau accumulation was highly correlated with memory‐related hippocampal activation. Greater tau accumulation and hippocampal activation were negatively correlated with memory performance. Neural activation in other task‐related structures was not correlated with local or global tau accumulation.ConclusionSimilar to observations in cognitively healthy aging, entorhinal tau accumulation is closely associated with hippocampal hyperactivity and impaired memory performance in MCI and mild dementia. Interestingly, this association is specific for medial temporal lobe structures.