ABSTRACT
Alzheimer's disease (AD), characterized by progressive cognitive decline, is the most prevalent neurodegenerative disease in the elderly. Cerebral ß-amyloid (Aß) 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 Aß 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 Aß deposition. The results with Aß deposition was compared with the serum levels of phosphorus. The subjects with cerebral Aß deposition showed lower levels of serum phosphorus than those without Aß deposition. Furthermore, multiple regression analyses showed that a low level of serum phosphorus correlated with cerebral Aß 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 Aß deposition in a cognitively impaired population.
ABSTRACT
OBJECTIVE: Although apolipoprotein (APOE) ε4 allele is a well-established risk factor for late-onset Alzheimer disease (AD), the mechanism of its effects on AD pathogenesis is not fully understood. We aimed to investigate the effects of APOE genotype on regional cerebral glucose metabolism in cognitively normal (CN) elderly. We further tried to elucidate whether or not such effects are associated with beta-amyloid protein (Aß) deposition. METHODS: 31 CN elderly participants underwent clinical examination, a range of neuropsychological tests, APOE genotyping, and Pittsburgh compound-B- and fluorodeoxyglucose-PET scans. RESULTS: 17 APOE ε4 carriers and 15 non-carriers were included. Both hypometabolic and hypermetabolic regions were observed in ε4 carriers compared with noncarriers when age, education, and sex were controlled. When the degree of global cerebral Aß deposition was adjusted, the hypometabolic regions in the temporo-parietal area (i.e., BA 22 and 39) largely disappeared, whereas the hypermetabolic regions persisted in medial frontal and anterior temporal areas (i.e., BA 38, 11, and 39). Behaviorally, verbal episodic memory scores of APOE ε4 carriers were slightly lower than those of noncarriers, though still within normal range. CONCLUSIONS: Our findings indicate that decreased cerebral glucose metabolism in the temporoparietal junction associated with APOE ε4 in CN elderly appears to be mediated by Aß deposition, and the effect of APOE ε4 on hypermetabolism in the frontal and anterior temporal regions is independent of Aß and may be associated with presence of compensatory mechanism in CN elderly with the ε4 allele.
