Abstract
Background: Neuritic plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer’s disease (AD), while the role of brain amyloid deposition in the clinical manifestation or brain atrophy remains unresolved. We aimed to explore the relation between brain amyloid deposition, cortical thickness, and plasma biomarkers.Methods: We used 11C-Pittsburgh compound B-positron emission tomography to assay brain amyloid deposition, magnetic resonance imaging to estimate cortical thickness, and an immunomagnetic reduction assay to measure plasma biomarkers. We recruited 39 controls, 25 subjects with amnesic mild cognitive impairment (aMCI), and 16 subjects with AD. PiB positivity (PiB+) was defined by the upper limit of the 95% confidence interval of the mean cortical SUVR from six predefined regions (1.0511 in this study).Results: All plasma biomarkers showed significant between-group differences. The plasma Aβ40 level was positively correlated with the mean cortical thickness of both the PiB+ and PiB- subjects. The plasma Aβ40 level of the subjects who were PiB+ was negatively correlated with brain amyloid deposition. In addition, the plasma tau level was negatively correlated with cortical thickness in both the PiB+ and PiB- subjects. Moreover, cortical thickness was negatively correlated with brain amyloid deposition in the PiB+ subjects. In addition, the cut-off point of plasma tau for differentiating between controls and AD was higher in the PiB- group than in the PiB+ group (37.5 versus 25.6 pg/ml, respectively). Lastly, ApoE4 increased the PiB+ rate in the aMCI and control groups.Conclusion: The contributions of brain amyloid deposition to cortical atrophy are spatially distinct. Plasma Aβ40 might be a protective indicator of less brain amyloid deposition and cortical atrophy. It takes more tau pathology to reach the same level of cognitive decline in subjects without brain amyloid deposition, and ApoE4 plays an early role in amyloid pathogenesis.
Highlights
The aims of the present study are the following: first, to evaluate whether cortical amyloid deposition is related to blood biomarkers and clinical manifestation of dementia; second, to elucidate the relation between amyloid deposition and cortical atrophy in individual brain regions; and third, to explore the effects of ApoE4 carrier status on cortical amyloid deposition in healthy control subjects, subjects with amnesic mild cognitive impairment (MCI) and subjects with Alzheimer’s disease (AD)
The percentage of ApoE4 carrier status was highest in the AD group, followed by the amnesic MCI (aMCI) group and the control group (Pearson Chi-square 6.348, P = 0.042)
We demonstrated in this study that cortical amyloid deposition, in terms of mean cortical SUVR (mcSUVR), explains more than 20% of the cortical thickness
Summary
Neuritic plaques composed of beta-amyloid (Aβ) fibrils and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau protein are the pathological hallmarks of Alzheimer’s disease (AD), the role of brain amyloid deposition in the clinical manifestation or brain atrophy of AD has been debated over decades.On the one hand (advantages), Aβ deposition has been associated with cognitive decline and neurodegeneration (Frisoni et al, 2009; Villemagne et al, 2013; Sevigny et al, 2016; Iaccarino et al, 2018; Jacobs et al, 2018) or even with emotional (Krell-Roesch et al, 2018) and behavioral symptoms (Marshall et al, 2013; Mori et al, 2014). Neuritic plaques composed of beta-amyloid (Aβ) fibrils and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau protein are the pathological hallmarks of Alzheimer’s disease (AD), the role of brain amyloid deposition in the clinical manifestation or brain atrophy of AD has been debated over decades. A recent functional connectivity study showed that brain regions involved in the default mode network (including the precuneus, posterior cingulate, and angular gyrus and medial prefrontal cortex) happen to be among the earliest brain regions of amyloid deposition. Neuritic plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer’s disease (AD), while the role of brain amyloid deposition in the clinical manifestation or brain atrophy remains unresolved. We aimed to explore the relation between brain amyloid deposition, cortical thickness, and plasma biomarkers
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