Abstract
Alzheimer's disease (AD), characterized by progressive cognitive decline, is the most prevalent neurodegenerative disease in the elderly. Cerebral β-amyloid (Aβ) deposition is the major pathological hallmark of AD. Recent studies also have shown that the serum level of phosphorus correlates to the risk of incident dementia. To date, the linkage between cerebral Aβ deposition and the serum phosphorus level remains unknown. In this study, we analyzed the levels of serum phosphorus in 109 mild cognitive impairment (MCI) and 73 AD dementia (ADD) subjects. All subjects underwent Pittsburgh compound B positron emission tomography (PiB-PET) imaging to measure cerebral Aβ deposition. The results with Aβ deposition was compared with the serum levels of phosphorus. The subjects with cerebral Aβ deposition showed lower levels of serum phosphorus than those without Aβ deposition. Furthermore, multiple regression analyses showed that a low level of serum phosphorus correlated with cerebral Aβ deposition, even when age, sex, apolipoprotein E ε4 genotype, and MMSE z-score were controlled for. Serum levels of other ions, including calcium, iron, zinc, and copper, showed no such correlation. In conclusion, our results suggest that the serum level of phosphorus may be used as an easily accessible blood biomarker for cerebral Aβ deposition in a cognitively impaired population.
Highlights
Alzheimer’s disease (AD) is one of the most disastrous neurodegenerative diseases and the most prevalent cause of dementia in elder population
The partial correlation analyses revealed a significant correlation between the serum level of phosphorus and the deposition of cerebral amyloid in both mild cognitive impairment (MCI) (r = −0.23, df = 105, p = 0.018) and AD dementia (ADD) (r = −0.26, df = 69, p = 0.031) groups (Figure 1A)
Serum phosphorus level was correlated with cerebral Aβ deposition even after controlling for serum calcium levels and/or Mini-Mental State Examination (MMSE) score with age, sex, and ApoE ε4 types
Summary
Alzheimer’s disease (AD) is one of the most disastrous neurodegenerative diseases and the most prevalent cause of dementia in elder population. Cerebral β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) are characteristics of AD (Hardy and Higgins, 1992; Scheuner et al, 1996; Wisniewski et al, 1997; Murphy and LeVine, 2010; Bloom, 2014). Even though Aβ pathology may not necessarily correlate with cognitive decline in a linear manner, accumulating evidence indicates that cerebral Aβ plays a critical role in AD pathogenesis and that neuritic plaques are specific characteristics of AD (Hardy and Higgins, 1992; Wisniewski et al, 1997; Nelson et al, 2009). It is crucial to determine whether cognitively impaired subjects, including mild cognitive impairment (MCI) or dementia patients, have cerebral Aβ deposition in order to diagnose the underlying AD accurately. Discovery of accessible biomarkers that reflect the degree of cerebral Aβ deposition would be very beneficial
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