Does hypertension contribute to tau load in Alzheimer\u27s disease? Cross-sectional positron emission tomography study using [11C]PBB3

Objectives: Hypertension is known to be a risk factor for dementia, including Alzheimer’s disease (AD). However, its pathological role in AD is unclear. This study aimed to investigate the influence of hypertension on the brain using tau deposition detectable by a novel positron emission tomography (PET) ligand, [11C]PBB3.Methods: Brain magnetic resonance imaging scans including susceptibility-weighted imaging (SWI), PET scans with [11C]PBB3 and [11C]PIB, and neuropsychological tests, such as the Mini Mental State Examination (MMSE), were performed on 55 subjects, including those with AD and mild cognitive impairments (MCI) and healthy controls (HCs). Subjects diagnosed with other types of dementia, such as vascular dementia, and those both aged 80 were excluded. In the PET imaging, standardized uptake value ratios (SUVRs) were determined as measures of radioligand retention using the cerebellar cortex as reference. Subjects were divided into hypertension-positive (HP) and negative (HN) groups based on clinical history, and comparisons were performed.Results: The HP group included 11 subjects with AD, 6 with MCI, and 7 HCs, while the HN group included 6 subjects with AD, 9 with MCI, and 16 HCs. The MMSE scores in the HP group were significantly lower than those in the HN group. Hypertension is associated with cognitive decline and increases in microbleeds (MBs) observed in SWI. These findings were consistent with previous reports suggesting that hypertension was a risk factor for dementia or cerebral vascular disease. The tau load observed by [11C]PBB3-PET was increased in the HP group overall. However, no significant difference could be observed in subgroups (HC, MCI, and AD) between HP and HN groups. When only the PIB-negative subgroup in MCI is taken into account, the tau load observed in [11C]PBB3-PET seems to be higher in the hypertension-positive group. (However, the size of the PIB-negative subgroup is very small.) In our hypothesis, hypertension may affect not only cerebral angiopathy but also tau load. However, when the amyloid load becomes remarkable with the onset of AD, it would influence cognition and AD pathology stronger than hypertension.Conclusion: Our study indicated that hypertension contributed to cognitive decline and increase in MBs associated with AD and that tau load observed in [11C]PBB3-PET was higher in the hypertension-positive group. Hypertension may modify tau load but to a lower extent than the amyloid pathology. Hypertension likely accelerates cerebral angiopathy and tau load, independently of amyloid load.AD/PD 201