Neurofibrillary tangle-predominant dementia followed by amyloid β pathology: a clinico-radio-pathological case providing insights into current disease-modifying therapeutic strategy

Neurofibrillary tangle (NFT)-predominant dementia/ primary age-related tauopathy (NFTD/PART) is an entity presenting with the deposition of NFT mainly in the medial temporal lobe.It is distinct from Alzheimer's disease (AD) in that it shows minimal deposition of amyloid β (Aβ) plaques [3,6,10].Recently, based on the amyloid cascade hypothesis, Aβ-targeting disease-modifying therapies (DMTs) for AD have been developed [9].The dilemma, however, is that Aβ deposition is observed frequently in the advanced ages regardless of the presence of AD [8].Thus, Aβ plaque accumulation can occur concurrently in patients presenting with other dementing conditions.This situation complicates the efficacy of DMTs, making accurate differentiation between conditions crucial for effective treatment, especially considering the high costs and potential side effects of DMTs.Here, we report a clinico-radio-pathologically-confirmed case that initially developed NFTD/PART and then gradually developed overlapping Aβ pathology, highlighting its importance in the context of DMTs.An 88-year-old man without a significant past medical history or family history of neurological disorders presented with mild cognitive decline (Mini-Mental State Examination [MMSE] score: 26/30).Bilateral atrophy and reduced radioligand uptake in the medial temporal lobes were observed on MRI and [ 18 F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), respectively (Fig. 1).At age 90, cerebrospinal fluid Aβ, phosphorylated tau, and tau levels were normal.[ 11 C]-Pittsburgh compound-B (PiB) PET,